Skip to main content

Full text of "Opening Statements Before the Committee on Appropriations"

See other formats


Brthe&ud, .auiyiaiid 20014 

-^ ^/ 1,-^iUl::^-^ a1 d^-!-.-^€ c^i^-jy iAn'^L' ^,pf2-'i.-^-pnyUiZ- 

Pcsblic laalth Service 
Ul.^ . Naeio»al Institutes of Health 

List of Witnesses 

Bre James As Shaataoa, Director^ Hatioiml Institutes of Health 

accoispaaisd by 

DSa Stuart M. Sessoms, Deputy Director, National I?iistitut@s 

of Health 
Br« G« BurrougSas Mider„ Dixeetor of Laboratories sad Gliaiesg 

Hatiosial Iiastitutes of Health 

Dr. John F» Sherman, Associate Director for Estraisural 

Programs j> National Institutes of isaltb 
Richard La Seggel, Executive Officer, iational Institutes of 

B« J. Sadesl^s Financial Haaagement Officer;, Matioaal lastitutes 

of Health 

Dr. Luther L« Terry, Surgeon General 
Harry Lo Boran, Chief Finance Officer 

James F. lelly, Departaent Gofiaptroller 

/ 1 

)S6 ? 


Statement by Director, National Institutes of Health 
Public Health Service 


1966 Appropriation Estimates 

Mr. Chairman and members of the Committee: 

I have always felt it to be one of my more congenial duties 
to appear before this Committee to report to you on the progress of 
the national effort in health research, to give an account of NIH 
stewardship in administering Federal support for biomedical research 
and to outline the future needs of the program as I see them. This 
is the tenth occasion on which I have had this privilege and I am 
therefore especially mindful today of the role which this Committee 
has played in stimulating medical research. The tremendous growth 
in the scope and substance of the NIH programs during the past ten 
years owes much to Congressional recognition of the importance and 
urgency of health research. 

Before proceeding further with my prepared statement, Mr. Chairman, 
it might be appropriate if I were to act on your suggestion and sketch 
out, for the benefit of the new members of this Committee, the 
background of the NIH programs, and their relationship both to the 
total national medical research effort and to the role which the Federal 
Government plays in its support. 

[Extemporaneous description of NIH programs and their role] 

_ 2 _ ^^H<i'^ ^ 

I should like to talk for a few minutes about the direction 
in which biomedical research seems to be moving and the role which 
Federal support programs — and the NIH programs in particular — 
might most usefully play in the years immediately ahead. I should 
then like to discuss some of our administrative problems and comment 
on the salient features of the NIH budget request that is now before 

The growth that has taken place in medical research involves 
much more than the increase in the size of the expenditure for its 
support of the number of people actively engaged in it. It has been 
a growth in the true biological sense of development. The medical 
research effort today is not merely larger than it was ten years ago, 
it is also more mature — in character, in outlook and in capabilities. 
The change that has taken place is, in fact, as significant as the 
transition from adolesence to adulthood. 

The biomedical research community in this country is now 
quite clearly entering a new phase which involves dramatic changes 
in its concepts concerning some of the major biological and disease 
problems, in the substance of the investigations it undertakes, in 
the tools and methods which it uses and in the social and economic 
framework within which it works. 

Biology is the most complex of the sciences and, because it 
involves life itself, the most difficult field for experimentation. 
It has therefore lagged behind the other sciences in reaching a 

- 3 - 

comparable stage of maturity. Progress along the broad frontier 
of science is never uniform and major advances take place, successively, 
in one or the other of its principal disciplines. Chemistry, for 
example, made tremendous strides during the 1920 's and 1930' s; physics 
was clearly the dominant science of the 1940 's and 1950' s. There is 
reason to believe — and certainly much reason to hope — that in the 
1960 's we have entered what may come to be called the age of biology. 

New knowledge, new techniques and, which is even more 
important, new ideas are changing the structure of biology as a science, 
are amplifying the power of medicine to deal with the problems of 
sickness, disability and premature death, and will in the foreseeable 
future alter the patterns of preventive and therapeutic medicine. 

These changes will require comparable changes in the collective 
community involvement in biomedical research, training and services 
of which the Federal support programs are an increasingly important 
feature. Scientific progress and societal support are reciprocal 
factors: as science progresses it makes more demands on society; 
as society broadens its support, science is able to progress more 

During the past ten years the NIH extramural programs have 
been primarily designed, on the one hand, to stimulate and support the 
work of individual investigators and, on the other, to build up the 
national capability for research. To the latter end we have been 

- 4 - 

concerned with research-training, primarily at the graduate levels; 
with early support for promising young investigators; with the 
construction and equipping of more adequate research facilities; 
and, in recent years, with the creation of new forms of integrated 
research organizations. 

These efforts have been outstandingly effective. No one 
who has watched the development of biomedical research during the 
past decade can fail to be impressed by its progress. There has 
been rapid and steady acceleration in the expansion of research 
capability; in broadening the scope of attack both on basic biological 
questions and on disease problems; in the pace of research productivity 
and achievement; and in heightening the quality of the work done. 

The lack of facilities and experienced research personnel is 
no longer the seriously limiting factor on the expansion of research 
that it was up to a very few years ago. Thanks in no small measure 
to the consistent interest of the Congress , this country now has varied 
and flexible means for biomedical research which, if existing programs 
are vigorously maintained, will continue to gain in strength and 
versatility. In other words, we need no longer be primarily concerned 
with laying the foundations for research — the main thrust of our 
efforts can now be devoted to mounting the comprehensive and massive 
attacks on disease problems and related basic research for which these 
foundations were designed. 

- 5 - 

This is not to say that we shall no longer be concerned with 
broad national needs for new resources and new facilities both 
for research and for training. The needs of graduate education in 
the biological sciences, in particular, are far from being met. 
We should, for example, stimulate and assist the new medical schools 
that are now coming into being to include in their plans adequate 
resources for graduate education. But, on the whole, we may now 
turn our attention to problems of balance and adaptability to 
changing opportunities . This will require us to become more 
selective in expanding our support programs. 

The directions in which Federal support for biomedical 
research should move must be related to an overall national plan 
and purpose which, on one side, encompasses activities in the 
prevention, diagnosis and treatment of disease and, on the other side, 
includes undergraduate, graduate and professional education and the 
whole gamut of scientific research activities. 

Within this broad context, NIH plays a dual role. By its 
organizational position as a bureau of the Public Health Service 
and the legislative language creating the various Institutes, NIH 
is properly described as a health organization using scientific 
research for the futherance of its particular health mission. At 
the same time, however, because of the nature of its activities and 
its special relationships with the academic community, NIH can also 
be regarded as a scientific research organization which has the 

- 6 - 

special mission of concerning itself with health problems. In 
its role as a health organization, NIH is an important adjunct to 
health service activities and, as its preoccupation with the creation 
of a research base recedes, it should be able to give more attention 
to the need to provide a better link between research results and 
their practical application. In its role as a scientific research 
organization, NIH has a significant involvement with university 
science departments and, as the science base of medical research 
broadens, NIH will inevitably be increasingly involved in the 
activities of a wider circle of the scientific community. These 
two spheres of interest are not necessarily in conflict but they do 
present problems of balance and seem likely, in the future, to 
complicate the task of effective policy and program development. 

The substance of science with which medical research must be 
concerned has expanded to a point where the traditional clinical 
disciplines no longer dominate the scene. Some of the most promising 
and productive work is today being done in fields that sprawl across 
the neat categories into which academic science has long been divided- 
The foresight of the Congress in providing support for a very broad 
range of fundamental research and training relevant to the health 
sciences has played a large part in fostering this widening of the 
thrust of biomedical research. 

- 7 - 

An outstanding example of the 'new look' in medical research 
is the move towards the intensive study of human development — 
viewing man as a single complex unit and his progression from 
conception to death as a single consequential continuum. There is 
ample reason to believe that such an integrated approach will not 
only shed fresh light on the origin, causes and courses of some 
diseases and disabilities but that it can make unique contributions 
to preventive medicine and to the solution of congenital and 
environmental health problems. 

There are exciting opportunities and provoking challenges on 
many biomedical research frontiers . 

Developments in the field of molecular biology have the most 
fundamental implications for medicine. It has been suggested — and it 
is no exaggeration — that its ultimate effects on the practice of medicine 
will be as revolutionary as the discovery only a hundred years ago 
that diseases could be caused by germs . 

The door to the inner workings of genetics has been pried open 
by such brilliant young scientists as Dr. Nirenberg of the National 
Heart Institute. We know enough to be reasonably sure that the 
intricate mechanisms controlling heredity also control — or at least 
influence — some aspects of the functioning of the organism throughout 
its life, probably including its predisposition to contract certain 
diseases. Much difficult work remains to be done — and, I may say, many 

inspiring hunches will be needed — before we have a sufficient 
understanding of the genetic process to be able to apply our 
knowledge to the prevention or cure of congenital disabilities 
or weaknesses. But the rewards of success appear to be so 
promising that this field merits close attention and consistent 
support . 

Although man has reproduced himself since the beginning of 
the species, the process by which this is accomplished is still so 
little understood that science is not prepared to give definitive 
answers to many of the urgent questions that now arise in connection 
with population control. 

The Committee has during the past few years heard much 
testimony concerning the ubiquitous role that viruses may be playing 
in a wide range of diseases not heretofore suspected of having a viral 
origin. The apparent ability of viruses to continue to affect their 
host even after they seem to have disappeared not only indicates the 
difficulties encountered in virus research but also illustrates how 
a research pursuit can be frustrated simply by the lack of techniques 
for keeping the culprit in sight. 

A beginning is now being made on the systematic study of 
environmental poisons — not only water pollution and air pollution but 
the cummulative affects of all kinds of chemicals and drugs which we 
breathe, swallow or touch in the course of our normal activites. The 
finger of suspicion has been pointed at some of these compounds not 
only as possible causes of disease but as having effects transmittable 
to our offspring. 

- 9 - 

While drugs are under surveillance for their possible dangers, 
the range of their effectiveness in the cure and alleviation of 
disease is constantly widening. This is particularly true in 
psychopharmacology which now holds out the hope that we may in the 
not too distant future be able to release a high proportion of the 
inmates of our mental institutions. 

The behavioral sciences are becoming a significant concern 
of medical scientists, as it is increasingly recognized that man 
reacts — physiologically as well as psychologically — to all aspects 
of his environment. As this Committee is well aware, juvenile 
delinquency is, in a sense, a disease — like alcoholism, drug addiction 
or overeating. The line between the medical sciences and the behavioral 
sciences is disappearing in many areas and medical research is again 
taking as its province the attainment of the Roman ideal of "Mens sana 
in corpore sano" — a sound mind in a sound body. 

A common feature of all these areas into which some of the 
major thrust of medical research is shifting is that they cut across 
the traditional categorical lines. It is already quite clear that 
much of the research effort of the future will be focused on fundamental 
biological processes whose disturbance (as, for example, by a virus) 
or malfunction (due, perhaps, to a genetic deficiency) results in a 
condition we recognize as a disease. Physicians have long known that 
treatment of the symptoms of a disease must, if possible, be accompanied 

- 10 - 

by treatment to remove its cause. Medical scientists similarly 
recognize that research focused on a disease must be accompanied 
by research into the biological process which underlies it. 
Research which starts with a normal biological process and explores 
the aberrations that result in disease is no less important to the 
advancement of medical knowledge — and is sometimes less difficult — 
than research which starts with a disease and seeks its causes . 
To achieve a proper balance between these two approaches must be 
one of our main concerns. 

Another common feature of current developments in medical 
research is its increasing reliance — or even dependence — on methods, 
tools and techniques not traditionally associated with biology and 
medicine. Highly effective use is made — though still by too 
limited a circle of investigators — of concepts and instrumentation 
borrowed or adapted from the physical sciences. The instrumentation 
developed by physicists is far more sophisticated and refined than that 
in common use in medical research. Automation offers possibilities 
for routine laboratory and even clinical procedures which are only 
beginning to be explored. 

The translation of biological phenomena into mathematical 
models presents a powerful tool for their systematic explorations — 
especially now that computer technology has made it feasible to perform 
extensive series of very complicated mathematical computations. The 
difficulty in this area is that there are, as yet, so few mathematical 

- 11 - 

generalizations in biology. There are so many variable factors 
and their relationships are so complex that it is extremely difficult 
to state them in mathematical terms. The work requires the combined 
efforts of biomedical scientists with a flair for understanding 
analogous mathematical concepts and mathematicians with a flair for 
understanding biological problems. Such teams are not easy to 
organize but can be most effective. 

The creation of a Division of Computer Research and Technology 
at NIH is a significant step in our efforts to being the precise 
techniques of mathematics and the capabilities of data processing 
machines to bear on the solution of biomedical problems. This 
Division and the National Heart Institute are in process of installing 
an experimental computation-data conversion system in the Clinical 
Center which should make it possible to examine systematically and to 
relate a large volume of data derived from instruments used in 
physiological experiments. The Division is also working with the 
Clinical Pathology Department of the Clinical Center is pioneering 
automatic handling of laboratory data and its rapid correlation with 
existing data. One of the most important functions of the Division, 
however, will be to bring biological and medical scientists into 
close personal contact with sophisticated mathematical, engineering, 
and systems competence. The new Division will provide our intramural 
scientists with a new and powerful tool but the training it will provide 

- 12 - 

not merely in the mechaaics of computer technology but in the 
underlying mathematical concepts may well be an even more important 
contribution to the long-range development of biomedical research. 

There is also considerable scope in medical research for 
investigators with engineering talents. The medical application of 
miniaturized electronic equipment needs to be further explored and 
there are opportunities for mechanical and materials engineers. It 
should, for example, be possible to develop a cheap and effective 
plastic mold to replace the heavy and clumsy plaster casts which are 
still used to immobilize certain parts of the body. 

A third feature of the changing methodology of medical research 
is the increased use of epidemiological studies and selective population 
surveys. These efforts, which can yield highly valuable results 
unobtainable through normal laboratory research or clinical investigation, 
often require the cooperation of statisticians, sociologists, social 
anthropol gists and, sometimes, even economic historians. 

I have tried to sketch very briefly some of the ways in which 
biomedical research is changing its complexion. Federal support for 
this research must recognize these changes and make allowance, within 
the terms of national policy, for meeting the changing requirements. 

One of the characteristics of research is that its costs 
usually increase as it matures. Each of the directions in which 
biomedical research is moving and the developmental programs which 

- 13 - 

will be necessary to incorporate research achievements into 
diagnostic and therapeutic practices will be costly. It must be 
expected that these costs will increasingly be reflected in future 
appropriation requests. 

The management of Federal programs to support health-related 
research or to facilitate its application to health services must 
take careful account of their impact on the participating institutions. 
These institutions usually have important functions and responsibilities 
that lie outside the fields with which the Federal programs are 
concerned. It is essential that they retain full responsibility for 
the management of their own affairs — that they have control over their 
education, research, and service activities; are free to implement 
their own plans for institutional development; and have first call 
on the professional loyalty of their faculty and staff. Special care 
must be taken to ensure that the expansion of facilities and growth 
of institutional activities stimulated by the Federal Government will 
take a form which will strengthen, rather than weaken, the total 
program, the organizational integrity, and the unique character of 
each institution. 

As you know, Mr, Chairman, some of the NIH programs — such as 
the institutional grants — are specifically designed to strengthen 
participating institutions while many others — including the various 
kinds of center grants — are implemented in a way that will have this 

- 14 - 

We also hope to develop administrative procedures which will 
give grantee institutions a more realistic role in the management 
of grant-supported projects. A pilot study is now underway in 
which responsibility for changes in project budgets or uses of 
grant funds, which normally require prior approval by the Public 
Health Service, has been delegated — with suitable guidelines — to 
the executive echelon of seven of the largest grantee institutions 
[the Massachusetts General Hospital, Massachusetts Institute of 
Technology, Columbia University College of Physicians and Surgeons, 
Rockefeller Institute, University of Pennsylvania, Johns Hopkins 
University School of Medicine, and the University of Michigan], 
The items covered by this arrangement are expenditures for office 
equipment, laboratory equipment costing more than $1,000, travel, 
hospitalization of patients, publication of books and monographs, 
tuition charges, and alterations or renovation up to a limit of $2,500. 
One of the purposes of the pilot study — ^which will be evaluated at 
the end of a year — is to develop procedures for assisting other 
institutions to improve their grants management. We believe that 
placing administrative authority for decisions of this kind in the 
hands of responsible administrators who are closest to the research 
activity, will not only improve the administration of grant funds 
but will better serve the scientific aims of the grant projects. 

- 15 - 

In giving increased attention to the institutional aspects 
of our support programs we are not, of course, losing sight of 
the importance of the individual grantees . Research is done by 
investigators — not by institutions or their administrators. The 
traditional NIH project grants must continue to be a major 
element in our program. 

Any comprehensive assessment of the projects supported by 
NIH grants will show — as several recent reviews have, in fact, 
shown — that the quality of the research done has remained impressively 
high. There has, very properly, been concern — in the Congress, in 
the scientific community, in the Executive Branch and, indeed, at 
NIH itself — that the rapid expansion of the Federal support programs 
might lead to lower standards for the work considered eligible for 
support. I am certain, Mr. Chairman, that the overall quality of 
research has not merely been maintained but has risen significantly 
as a direct result of the expansion of the project grant programs. 

I am happy to say that the quality of the work done by our 
grantees is fully matched by our intramural staff. 

The maintenance of the stature of NIH as one of the 
outstanding research institutions in this country — and, indeed, in 
the world — is, of course, of great importance to the national medical 
research effort. The highly-qualified and dedicated scientists and 
technical staff who work in the Clinical Center and the NIH laboratories 

- 16 - 

in Bethesda, in Montana, in Panama, in Ghana, in Pakistan and, 
on special assignment, in other laboratories around the world are 
making significant contributions to the progress of biomedical 
science and its success in the constant battle against the onset 
and effects of disease. That these contributions are widely 
recognized and respected is shown by the awards and honors which 
NIH scientists continue to receive. For example. Dr. Marshall 
Nirenberg, who has already been widely honored for his major 
contribution to the understanding of the mechanics of genetics, 
was one of eleven scientists to whom the President awarded the 
National Medal of Science. The Bolivian Government has named a 
hospital and erected a bronze statue in memory of the late 
Dr. Henry K. Beye who, as director of the Middle American Research 
Unit, led the fight against Bolivian hemorrhagic fever. 
Dr. Willy Burgdorfer, of the Rocky Mountain Laboratory, received 
a John Simon Guggenheim Memorial fellowship for his distinguished 
work on viral and rickettsial infections. 

I should like, if I may, Mr. Fogarty, to place in the record 
a listing of the awards received by members of the NIH scientific 
staff for the outstanding job they are doing. 

The quality of the intramural research at NIH is equally 
important to the maintenance of the quality of the extramural 
programs . This works in two ways . The presence on the Bethesda 

- 17 - 

campus of a cross-section of clinical investigators and bench 
scientists who are working in the forward areas of the research 
frontier makes it possible for those responsible for the direction of 
the extramural programs to keep abreast of new research developments, 
to spot new research opportunities, and to anticipate future research 
trends. In a field which is developing as rapidly as biomedical 
research and which involves so many scientific disciplines and 
specialties, this relationship is essential to sensitive and responsive 
policy development and program management. The fact that this 
relationship exists at NIH and the acknowledged standing of NIH as a 
first-class research institution also serves, in a subtle but very real 
way, to make the biomedical research community more responsive to 
NIH leadership in developing national programs. 

I am, however, very much worried, Mr. Chairman, about our 
ability to maintain high standards of scientific and administrative 
competence by the difficulties we have encountered in recruiting 
senior staff. The sort of persons we should like to have to develop 
new concepts and new approaches in an extremely broad and complex 
research area, can command much higher salaries — and with more 
attractive fringe benefits — in an academic institution than we are 
able to offer. The salary handicap is, for example, seriously affecting 
our ability to staff the new Division of Computer Research and 

- 18 - 

The effectiveness and viability of the NIH role in 
biomedical research — and, therefore, to a very large extent, the 
effectiveness of the whole national health research effort — ^will 
be significantly influenced by the quality of the professional 
staff in both the intramural and extramural programs. It is 
therefore essential that we should be able to recruit staff who 
not only have outstanding scientific and administrative competence 
but the vision to see the opportunities that lie ahead, the 
imagination to design fresh approaches to exploit those opportunities 
and the qualities of leadership necessary to insure that those 
approached are vigorously pursued. 

The budget estimates for the Institutes and operating 
Divisions of NIH total $1,040,056,000. This amount represents an 
increase of $74 million, or about 7 percent, over the expected 
operating levels for the current year. 

This budget, together with the funds that have been 
separately requested for Health Research Facilities Construction, 
direct construction, and the international activities using P.L. 480 
funds, provides for a third year of restrained and selective growth 
following seven years of extraordinarily rapid expansion of the 
programs. The increases requested are focused on specific targets 
in areas of science in which progressive expansion seems most 
desirable — such as gerontology, child health, and toxicology. 

- 19 - 

An increase of $25 million — or about 6 percent — is requested 
for regular research project grants. Of this amount, approximately 
$19 million will enable us to meet commitments for the support of 
existing research projects (that is, noncompeting continuations). 
The other $6 million is requested to bring indirect cost payments 
by NIH into line with the current practice of other Federal 
grant-making agencies . 

Increases totaling $18 million — or a little over 15 percent — 
are requested to strengthen the special research programs. Clinical 
research and special resource centers are playing an increasingly 
important part in extending this country's research capabilities to 
meet the challenges and exploit the opportunities that lie before us. 
The budget contains $57 million for these programs — an increase of 
$9.5 million, or nearly 17 percent, over their present level. 
The budget also includes an additional $6 million for the further 
expansion of the special grant program of the National Institute of 
Mental Health for hospital improvement. This program was started in 
fiscal year 1964 with an allocation of $6 million; the current 
allocation is $12 million; it is requested that $18 million be 
provided for fiscal 1966 for this important step in increasing the 
effectiveness of the treatment of mental illness. 

- 20 - 

Two new programs focused on areas in which there is both 
a great public need and a great scientific opportunity are included 
in the budget now before you. One is a request by the National 
Cancer Institute for $1.5 million to set up child leukemia centers. 
No cure for this tragic disease has yet been found but the curtains 
of mystery hiding its cause seem to be parting. The proposed 
centers will materially assist in accelerating leukemia research. 
The second new budget item is the proposal of the National Institute 
of General Medical Sciences to launch a program aimed at creating new 
resources for research and associated training in the fields of 
toxicology and pharmacology. As this Committee pointed out in its 
report on last year's appropriation bill, these two fields 
represent a deficiency in the NIH research programs — especially in 
the light of mounting evidence that prolonged exposure to many chemicals 
and drugs now common in our environment may have long-term effects on 
health and, possibly, on heredity. The budget includes $1 million 
for this program. 

The budget includes an increase of a little over $19 million — 
or about 8-1/2 percent — for the fellowship and training grant programs. 
Over half of this increase is in the training grant programs of the 
National Institute of Mental Health. The major increases among the 
other Institutes are: a little over $3.6 million for the National 
Institute of General Medical Sciences (of which $1 million is for 
predoctoral fellowships); exactly $2 million for the National Institute 

- 21 - 

of Child Health and Human Development; and about $1.5 million each 
for the National Institute of Arthritis and Metabolic Diseases and 
the National Institute of Allergy and Infectious Diseases. 

Considered by activity, two-thirds (or more than $13 million) 
of the requested increases for fellowships and training are to 
permit the funding of 165 additional graduate training grants 
bringing the total of these vitally important training projects to 
3,373. A substantial increase — about $4 million or nearly 23 percent 
over the current appropriation — is also sought for Research Career 
Development awards. This program, launched in fiscal year 1962, has 
amply demonstrated its effectiveness. The increase requested will 
permit 166 additional awards bringing the total number of current 
awards to 1,119. 

The increases requested in the budget now before you are 
modest but they will enable us to maintain the momentum of the present 
programs. It is, however, a tight budget with no slack in any of its 
components. It is, therefore, important that we have some flexibility 
in administering the NIH appropriations. Unforeseen developments are 
a normal feature of effective research, Mr, Chairman. In fact, if 
there were no unforeseen developments in the program of a research 
institution , I would begin to suspect that the institution was 
stagnating or doing very routine work. A vigorous research organization 
playing a major national role in a period of rapid scientific 

- 22 - 

developments cannot function as effectively as it should if it is 
bound too tightly to the details of budget estimates prepared 
twelve to eighteen months in advance. 

The degree of flexibility necessary can be achieved by the 
provision, in the Bill now before you, authorizing the transfers up 
to 5 percent between NIH appropriations and by the removal of 
present limitations on reallocations within each of these 
appropriations. I should like to urge the Committee to give its 
most sympathetic consideration to these two requests. 

During the past year there have been a number of changes 
among the directors of the Institutes and Divisions who will testify 
on the details of the various budget estimates. 

Dr. Robert H. Felix has been succeeded as Director of the 
National Institute of Mental Health by Dr. Stanley F. Yolles. 
Dr. Yolles joined the staff of the Institute in 1954, He became 
Associate Director for Extramural Programs in 1960 and for the past 
year and a half has been its Deputy Director. 

Dr. Clinton C. Powell, the first Director of the new National 
Institute of General Medical Sciences, has been succeeded by 
Dr. Frederick L. Stone who has been associated with the NIH 
extramural programs since 1958 including four years as Assistant 
Chief of the former Division of General Medical Sciences. He became 
Chief of the Division of Research Facilities and Resources when that 
was created in 1962. For the time being. Dr. Stone will continue to 
act in the latter capacity also. 

- 23 - 

Dr. Justin M. Andrews, the director of the National 
Institute of Allergy and Infectious Diseases, has retired. 
The new director is Dr. Dorland J. Davis who has been the 
Institute's Associate Director for Intramural Research 
since 1956. 

Dr. Charles V. Kidd has been succeeded as Chief of the 
Office of International Research by Dr. Charles L. Williams, Jr., 
who has been Associate Director for International Relations in 
the Office of International Health in the Office of the Surgeon 
General . 

I shall, of course, be happy to answer any questions which 
the Committee may have. 

Thank you, Mr. Chairman. 

Public Health Service 
General Research and Services 

List of Witnesses 

Dr. James A. Shannon, Director, National Institutes of Health 

accompanied by 

Dr. Frederick L. Stone, Acting Chief, Division of Research 

Facilities and Resources 
Robert H. Grant, Assistant Chief, Office of International 

B. J. Sadesky, Financial Management Officer, National Institutes 

of Health 

Dr. Luther L. Terry, Surgeon General 
Harry L. Doran, Chief Finance Officer 

James F. Kelly, Department Comptroller 


Statement by Acting Chief, Division of Research Facilities and Resources 

National Institutes of Health 
Public Health Service 


"Division of Research Facilities and Resources" 

The Division of Research Facilities and Resources administers grants 
vjhich support construction of new buildings or extensive renovation, clinical 
research facilities, centralized research resources such as computer centers, 
regional primate research centers, and other indispensable resources which 
meet the needs of many biomedical disciplines and many groups of scientists. 

Although the Division is responsible for five programs, only three will 
be discussed here. Funds for the health research facilities program and the 
general research support program are considered under separate appropriations. 

General Clinical Research Centers 

The general clinical research center is a clinical resource which enables 
the research findings of the laboratory to be brought to the practicing phy- 
sician. Although the first of these centers opened its doors less than five 
years ago, the program has already brought to the practice of medicine new 
techniques and new knowledge in patient care and treatment. 

As of January 1, 1965, 80 centers with a total of almost 1,000 research 
beds had been approved. Of these centers 68 were already in operation on 
December 30, 1964, in 66 institutions in 30 states, the District of Columbia, 
and Puerto Rico. 

Each center, a separate unit with a specific number of beds, has its 
own staff of nurses and technicians, its own laboratories and other supporting 
facilities, where scientists from many disciplines work together, carrying out 
Intensive, exacting clinical research. Such a facility makes possible the 


rigid control and all of the precise laboratory tests necessary for the conduct 
of excellent clinical studies in a wide range of human diseases and disabilities. 

In addition to the adult clinical centers--which may also admit children-- 
there are centers specially devoted to the investigation of diseases in child- 
ren. There is even a center for premature infants. The research in another 
center focuses on acute conditions such as burns, shock, and strokes. A 
chronic disease center Is investigating the problems of long-term illness and 
incapacitating conditions, a category which places great demands on the medical 
profession. A maternal-child center vi;lll investigate medical problems associ- 
ated x^ith pregnancy, birth, and infancy. 

More than 1,200 research studies are currently being conducted, an 
average of over 20 projects at each center. 

Although the center grants provide the facilities and supporting staff 
that make possible the research, the projects themselves are many times sup- 
ported by funds from various public and private sources. There follow a few 
examples of these projects which illustrate the broad variety of biomedical 
research conducted in these centers: 

Researchers studying the problem of narcotic addiction have shown that 
so-called incurable addicts can be maintained on methadone, a synthetic 
agent related to the morphine group of drugs, without the usual need to 
Increase dose and without the exhilarating effects which cause the tempta- 
tion to revert to using heroin. These patients are able to take this long- 
acting drug orally, engage in productive occupations and participate in 
rehabilitation programs. Rockefeller Institute, New York City. 

At another institution, workers found that 5-f luoro-uracil, an agent 
developed for the treatment of Internal malignancy, had selective 
destructive effect on certain skin lesions, such as senile keratoses, 
when applied as an ointment. University of Arkansas, Little Rock. 

Studies are being carried out in one clinical research center to evaluate 
the effectiveness of cross circulation of blood in humans. This techni- 
que involves the direct connection of major arteries and veins between 
two patients. If the patients are carefully matched according to major 
blood groups, the technique has been found to be relatively safe. As a 

result, it is possible to treat two patients with different disease 
states; each one having a normally functioning organ system such as 
kidney, liver, heart-lung, or bone marrow which substitutes for a mal- 
functioning counterpart in the other partner. University of Washington, 

Cardiologists have been working on the problem of reduction of fatality 
from myocardial infarction, the cause of 450,000 deaths in the United 
States annually. By working out careful monitoring systems to detect 
dangerous changes in the electrical conduction of the heart, these 
workers have been able to use the cardioverter unit which they previously 
developed and, thereby, reverse these dangerous electrical discharges 
at critical times, reducing mortality. Peter Bent Brigham Hospital, 
Bostcn, Mass. 

Studies of lead poisoning and its treatment have resulted in a method of 
measuring the body's lead stores by analysis of bone marrow biopsy speci- 
mens. The effectiveness of removal of lead from the body by chemical 
agents can also be evaluated by this technique. University of Pittsburgh, 

It can be anticipated that from the research conducted in these centers 
will continue to come the new basic clinical knowledge and medical achievements 
essential to continued progress in combating disease. 

The request of $28,500,000, an increase of $1,585,000 over 1965, will 
provide for continued support of existing centers and provide for some in- 
creased costs of those centers. 

Regional Primate Research Centers 

The regional primate research center program, originally confined to 
further research in heart diseases, has been expanded to include the primate 
as a major resource for research in all biomedical disciplines in the solution 
of health problems in man. 

Of the seven primate research centers, six regional and one national, 
four are completed. All have initiated their research programs. 

While differing in design and layout, depending on its scientific 
mission, each center is a model for the care, housing, and humane use of 
laboratory animals. Facilities of all the centers are available to scientists 
throughout each region as well as to visiting scientists from other parts of 
the country. 

Although the centers are engaged in a variety of research programs 
each has a special interest area. 

The National Center for Primate Biology, at the University of California 
at Davis, is unique among the seven centers, conducting studies in which 
the primates themselves are not only a biomedical laboratory tool but are 
the object of the research. 

The Oregon Regional Primate Research Center at the University of Oregon, 
dedicated in 1962, is fully operational. Investigations in reproductive 
physiology receive special emphasis at this center. 

Wisconsin Regional Primate Research Center at the University of Wisconsin 
was completed in April 1964. Psychology, mental retardation, and related 
studies are of particular interest in research programs at this center. 

The Delta Regional Primate Research Center at Tulane University, New Orleans, 
xjas completed in November 1964. One of its important research areas is 
infectious diseases with particular attention to the study of viral 

The Regional Primate Research Center at the University of Washington was 
completed in December 1964, and its research projects are T,7ell underway. 
Research in neurophysiology and other physiological research are of 
particular interest at this center. 

The construction plans for the New England Regional Primate Research 
Center at Harvard University have been approved. Research programs in 
temporary facilities emphasize virus diseases and parasitic infections. 

At the Yerkes Regional Primate Research Center at Emory University, 
Atlanta, construction is underway, with completion scheduled for 1965. 
Meanwhile, the nucleus of the long-range scientific program has been 
established and research has proceeded in a variety of studies which 
at this center are related to, and utilize, the great apes. 

To provide continued support for operations and for the core research 
program of the seven regional primate research centers the request for 1966 
is $7 million, the same as in 1965. 

Special Research Resources 

Special research resources are large-scale, costly facilities essential 
to modern sophisticated research, influencing its conduct and benefiting the 
entire institutional or regional research capability. They place pox^erful 
tools and techniques in the hands of the biomedical researcher. 

Support of these resources is imperative, but they must be established 
as centralized facilities available to a wide community of biomedical research- 
ers to permit full time use of the equipment and lower the ultimate cost of 
each project. 

Examples of such resources are computer centers; biomedical engineering 
and scientific communication facilities; and biological material supplies. 
As of December 1, 1964, this program supported 59 such centralized resources 
including 32 computer centers. 

Biomedical computer centers speed the collection, processing, and 
evaluation of data, and make possible new conceptual approaches to knotty 
research problems. Without computers many promising leads in health research 
could not be followed. 

Illustrating the diversity of research projects supported by this 
program are the following examples: 
Computer Centers 

A digital computer has dramatically increased the accuracy and control in 
the radiation treatment of cancer and reduced unplanned over-exposure and 
its attendant damaging effects. It is also permitting an attack on the 
problem of providing optimum conditions for radiation treatment for each 

The blind are enabled to work professionally on computers using new basic 
techniques and devices developed through unique research conducted at a 
computer center. These developments have already been incorporated in 
training programs in Pittsburgh, Boston, and Los Angeles. 

In the area of mental health, a hospital-based cooperative drug screening 
program is attempting to select the most effective drug for any given 

Biomedical Engineering Center 

Situated at Northwestern University this resource applies the principles 
and know-how of engineering sciences to the complex problems of biology and 


A major biomedical engineering area includes investigations into charac- 
teristics of nev7 materials from which improved artificial organs such as 
kidney, lungs, and other patient support systems might be constructed, 
as well as practical studies to evaluate a compact artificial heart 
pump requiring only a small volume of blood to prime the system. 

Another program at this center currently undergoing pilot tests seeks 
early diagnosis of cardiac defects in young school children based upon 
characteristics of the heart sounds. 

A few biomedical engineering centers are in the planning stage; others 
have submitted applications which are under review. 

This type of center requires blending of the talents of engineers, 
biologists, machinists, physicians, and many others in a complex administra- 
tive structure at the institutional level. 
Information Centers 

The scientist is confronted by masses of data and printed material 
which must be evaluated, incorporated into research programs, and used to 
develop new approaches to research problems. Although data retrieval and 
information processing systems exist at the present time they have not yet 
been adequately developed. Support of the fundamental sciences of cummuni- 
cation and information is necessary to develop large-scale systems and to 
implement major retrieval apparatus. Such studies are now supported at 
Western Reserve, Washington University, and the University of Pittsburgh. 
Review of other applications is underway. Results from these grants are 
expected to lead to the design of more efficient systems and better service 
to the individual scientist. 
Other Special Resources 

The long-term administration of potent drugs has become commonplace in 
medicine. Data from fundamental studies must be utilized to obtain general- 
izations about the metabolism, distribution, and mechanism of action of 
these drugs for anticipating adverse drug reactions and assessing the 

potential hazards as well as possible benefits of new drugs. There has been 
a proliferation of new environmental and economic chemicals resulting in a 
widespread environmental contamination that poses unevaluated threats on 
repeated exposure. A toxicology and biochemical pharmacology resource is 
being established to expand our national competence and to meet the need for 
increased knowledge of long-range toxic effects of new drugs and other chemicals. 

The world-recognized American Type Culture Collection is supported in 
its program of collection and distribution of authentic reference cultures of 
bacteria, viruses, mammalian cells, and other selected living organisms and 
materials needed by the national and international community of biomedical 

At Washington University in St. Louis, new computer programs and projects 
increasingly illustrate the versatility of the LING computer, a computer 
specifically developed for biomedical clinical and laboratory use. The impli- 
cations of this development for the future course of biomedical research have 
already excited broad interest in the scientific community. 

The New England Regional Enzyme and Biopolymer Resource conducts large- 
scale isolation, characterization, and production of specialized biochemical 
materials, including such biopolymers as thiophorase and lactic acid dehy- 
drogenase, for use in laboratory investigations. These materials which cannot 
be found at any commercial source must meet exacting standards, and applica- 
tion for them must be reviewed for scientific need by an outstanding scien- 
tific advisory board. 

To provide funds for special research resources already supported and 
for the development of 18 new resources, a budget of $12,150,000 is requested 
for 1966. The new resources include: scientific and technical information 
centers for expanded service in the communication of biomedical information; 


specialized animal research resources; and additional capabilities in the 
fields of computation and data processing, biomedical engineering, and 

An amount of $1,500,000 is included as part share in the collaborative 
study with the National Science Foundation to establish a national Drug 
Information Center. This resource is vital in providing scientists and 
clinicians with information on biological and clinical actions of chemical 
compounds . 

In conclusion, Mr. Chairman, the request for the Research Centers and 
Resources programs in the General Research and Services appropriation is a 
total of $51,254,000, as compared with $44,139,000 in 1965. This is an 
increase of $7,115,000 over 1965. 

# # # 


Statement by Chief, Office of International Research 
National Institutes of Health 
Public Health Service 


"Office of International Research" 

The Office of International Research was established within the 
National Institutes of Health to provide a focal poin; for policy for- 
mulation and guidance and coordination for all NIH international activi- 
ties. This office is responsible for the administration of the Interna- 
tional Centers for Medical Research and Training grants. International 
Postdoctoral Fellowships Program, the International Research Career 
Development Program, the SEATO-Cholera Research Program and the Special 
Foreign Currency Program. In addition, this office administers the NIH 
overseas offices which are engaged in developing and gathering information 
related to the NIH foreign activities. The estimates for these programs 
are contained in this appropriation, with the exception of the Special 
Foreign Currency Program which is presented in a separate appropriation. 

International Centers for Medical Research and Training 
The National Institutes of Health program of International Centers for 
Medical Research and Training has been established in response to the 
objectives outlined by the Congress under the International Health Research 
Act of 1960 (P.L. 86-610). The law seeks "to advance the status of the 
health sciences in the United States and thereby the health of the American 
people through cooperative endeavors with other countries in health research 
and research training." 

The ICMRT instrumentality represents such a cooperative endeavor, 
supported by NIH research grant awards to U.S. universities, in which 
highly stable research and research training centers have been developed 
at domestic and foreign affiliate sites to conduct medical investigations 
relevant to U.S. domestic research interests. The development of this 
series of international centers has created unusual opportunities for 
American physicians and scientists to pursue productive research careers 
in a foreign setting. A corollary is the stimulus the ICMRT program has 
provided to scientific personnel within the collaborating foreign affiliates 
to develop additional medical research and training resources in the 
participating host countries. 

Experience with the program indicates that the ICMRT is an effective 
mechanism for developing international scientific manpower, for strengthen- 
ing international operations already in progress, for providing basic 
research facilities and resources which upon invitation may be utilized 
by other U.S. university investigators, and for enhancing relations among 
participating institutions and agencies in the United States and abroad. 

Utilizing the international capabilities of scientists representing 
many disciplines, integrated and comprehensive programs for the study of 
all health problems, as well as those relating to medicine in the tropics, 
have emerged from the Centers located in Colombia, Costa Rica, India, 
Malaysia and Pakistan. For example, the scope of the University of Maryland 
program in Pakistan, initially limited to studies of gastro-intestinal 
infection and parasitology, has now been expanded to include medical entomology, 

nutrition, pediatrics, rickettsiology, bacteriology and epidemiology. 
Similar multidisciplinary programs have been developed at each of the 
other centers. 

A modest award has been made to the Ohio State University to conduct 
a study of the feasibility of establishing an ICMRT in Africa. This 
study will be undertaken in Nigeria to determine the potential for 
developing a research unit affiliated with the University of Ibadan and 
its medical faculty. Should the creation of an International Center in 
Africa prove practicable, planning funds will be made available from this 
year's appropriation request to the sponsoring university. 

International Postdoctoral Fellowships 
International Postdoctoral Fellowships have been awarded since 1958 
to support the training of promising foreign scientists for careers in 
biomedical research. Although these fellowships which permit foreign 
investigators to work for a period of a year or two in collaboration with, 
and in the laboratories of, American scientists in the United States, help 
to strengthen research capabilities in other countries, the purpose of 
the program retains a basically domestic orientation. These fellowships 
enrich post-graduate training in the biomedical sciences in the United 
States by enabling foreign investigators to share their ideas and background 
with American colleagues while working together in a common research environ- 
ment. In addition, the program provides the setting for foreign scientists 
to participate in research bearing upon the health needs of the American 

people, thus initiating investigations which are frequently continued and 
extended upon return of the Fellow to his home country. International 
fellowships, therefore, not only enhance opportunities for future collabo- 
rative research, but also help to strengthen research environments abroad 
to which American scientists frequently go to pursue specialized training 
in the health sciences. 

International Research Career Development 

A variety of unusual or unique opportimities exist in foreign countries 
to pursue studies of substantial importance to medical science and to the 
health of Americans. Investigations in the field of geographic patho- 
logy and epidemiology on an international basis are likely to continue 
to provide important clues to the causes of certain diseases which cannot 
be studied adequately in more restricted environments. 

To meet the needs of the Public Health Service for capable investiga- 
tors with foreign research experience, the National Institutes of Health 
International Research Career Development is providing opportunities for 
promising young scientists to work abroad as members of established research 
groups. This program provides for the assignment of 10 Public Health Service 
Commissioned Officers each year to research projects and programs overseas 
and fulfills an important need of the Public Health Service for highly 
skilled manpower with international experience. 

SEATO -Pakistan Cholera Research Program 

This program, administered by the Office of International Research, 
is a cooperative endeavor between the SEATO nations with funds being 
furnished by those nations. The Special Foreign Currency Program at NIH 
has made and will continue to make sizeable investment in the Research 
Laboratory in Dacca, Pakistan. This Laboratory, staffed with scientists, 
technicians and supporting personnel from the United States, Pakistan 
and other countries has developed a multidiciplinary attack on the problem 
of cholera. 

Overseas Offices 

The Overseas Offices of the NIH in Paris, France; Tokyo, Japan; and 
Rio de Janeiro, Brazil and science representatives in London, England 
and New Delhi, India have been established to carry out the following 

(1) Advance the program and policy interests of the NIH, and 
the scientific knowledge, training, and research objectives of 
individual U.S. scientists or U.S. scientific institutions. 

(2) Execute NIH responsibilities in respect to active, pending, 
or planned research projects, and in relation to research objectives 
generated through the NIH Intramural or extramural programs. 

(3) Participate in assessing the value of international meetings 

to decide which should have NIH representation and what type of repre- 
sentation would best serve the interests of NIH and its programs. 

(4) Provide NIH with information on scientific interests, capa- 
bilities, and resources available in other countries to solve mutual 
problems and promote mutual interests. 

Significant information has already been accumulated in regard to our 
investment in the United Kingdom, Sweden, France, Israel, Brazil, Chile, 
Peru, Japan, and a number of other countries. This information is being 
disseminated to our Institutes and Divisions which support research, abroad. 
This will permit a more effective review of foreign research grant applica- 
tions . 

The 1966 request for the Office of International Research is $5,998,000, 
an increase of $85,000 over the comparable level in 1965. 


Statement by Director, National Institutes of Health. 
Public Health Service 


"Division of Computer Research and Technology" 


The Division of Computer Research and Technology was established late 
in fiscal year 1964 in recognition of the great potential benefits to be 
derived from the intensive and comprehensive application of computer tech- 
nology and related disciplines to NIH research programs. The Division has 
been structixred to provide an integrated program of mathematical, statis- 
tical, and engineering research and development oriented toward the 
application of these sciences to the use of computers in the solution of 
biomedical problems. The funds being requested will be used primarily to 
support this research and development function. The Division also has a 
computation and data processing service function which is supported through 
the NIH Service and Supply Fund. 

Ongoing Projects 
Altho-ugh the programs of the Division are not yet operational, there 
are a number of projects now in being or soon to begin at NIH which are 
significant for, or suggestive of, the direction that the prcgrams of the 
Division might eventually take. One of these is an effective computer 
training program designed both to assist individual scientists with the 
application of computers to their ongoing research projects, and to stim- 
■ulate among the scientific staff in general a wider intei^st in the 

present and potential uses of computers in biomedical research. The im- 
portance of this training for the future of automatic data processing at 
NIH cannot be over-stressed. It is indispensable to the creation within 
the scientific community of an enlightened and responsive attitude toward 
the possibilities opened up by this new technology. 

Another ongoing program of real significance, and one that is espe- 
cially indicative of the way in which the medical scientist and the com- 
puter specialist can be joined in a cooperative research venture, is the 
hybrid computation-data conversion system to be installed in the Clinical 
Center in early calendar year 1965. This system, a combined ;indertaking 
of the Division of Computer Research and Technology and the National 
Heart Institute, is the most important single step taken to date to apply 
the capabilities of computer technology directly to the laboratory environ- 
ment and to the solution of NIH biomedical research problems. It will 
malce possible the selective processing of large volumes of diverse data 
derived from sensing instruments used to measure the results of physiolog- 
ical experiments. The intent is that this will be merely the first of a 
nnTTihpr of projects designed to provide versatile and efficient methods of 
data handling which are well suited to the needs of the biological scien- 
tist and which promise to expand greatly his potential for accomplishment. 

The Clinical Pathology Department has undertaken a pioneering venture 
in the automatic retrieval of laboratory data and its rapid correlation 
with already existing data. The computer system utilized in this program 
will maie possible the automatic assay of enzymes and the partition and 
distribution of blood and serum samples in response to a great number of 
varied requests submitted daily. The mathematical, engineering, and 


systems competence which Tirill be made available through the Divisicai of 
Computer Research and Technology will play an important role in the 
success of this and similar projects , 

Fyog??api, PJ,Etf3p 

Despite the excellent begiimings already made toward the application, 
of computer technology at NIH, it is believed that the organizational 
stat-ure, professional expertise, and versatility which will characterize 
the new Division will make possible far more dramatic advances in this 

Exploration of the applicability of mathematics and machine comput- 
ing and data processing to bioscientific problems is just beginning, and 
a well-rounded program, including the development of expertise in many 
related disciplines is needed. 

At the interface between coniputer science and mathematical statistics, 
promising possibilities are beginning to emerge for major new developments 
in statistical theory, with important implications for a wide variety of 
experimental design problems. Application will require extensive computer 
programming research and development, in which the new Division will play 
the leading role. 

The problems of communications between man and machine, especially 
in the dcanain of the life sciences, are and will remain challenging for 
some time to come. The Division is expected to conduct an intensive re- 
search program in this area with a view to coupling NIH programs effec- 
tively to rapidly advancing equipment designs. 

One of the most hopeful and urgent approaches to achieving significant 

progress in the application of computer technology to NIH programs will 
be the Initiation of cooperative studies involving Division staff and 
scientists in the Institutes. The areas of collaboration which could 
p2?oduce results of g2?eat significance for the NIH research program are 
many: the expansion of work on mathematical models of biological systems 
designed to provide usefiil medical research approaches and potential diag- 
nostic tools; enhancement of the capabilities and productivity of individ- 
ual scientists through the rapid conversion of laboratory data to forms 
that pennit efficient computer processing and analysis; development of 
retrieval systems to provide wider and more rapid access to and dissemina- 
tion of scientific information relevant to specific research -undertakings; 
exploration into the use of computers to provide pattern recognition 
capabilities for such p-urposes as the interpretation of X-rays and the 
automatic scanning of laboratoiy specimens; automatic retrieval of labora- 
tory information for programs such as clinical pathology, and th.e correla- 
tion of results with previous data on demand. 

Since fiscal year 1966 will be the first full year of operation for 
this Division, it is planned to give primary emphasis to extensive staff 
recruitment and development which will nake possible the first significant 
steps toward the activation of substantive Division programs in the areas 
of endeavor outlined above. The recruitment program presents a great 
challenge, and its success will be crucial for the attainment of the 
objectives for which the Division has been established. All of the prin- 
cipal job talents needed — mathematicians, statisticians, programmers, 

engineers, systems analysts — are in extremely short supply. Moreover, 
the essentially pioneering nature of many of the programs envisioned 
■will require that the Division attract only the "best of the talent that 
is available. Because the emergence of computer technology and of many 
of the related specialized disciplines that have evolved around it is a 
relatively recent phenomenon, it is anticipated that the staff nucleus 
in most of the major program areas of the Division— and most certainly in 
the mathematical, statistical, and engineering areas — will be ccairprised 
of comparatively young Ph.D's who have a special interest in the applica- 
tion of their specific disciplines to the life sciences. 

The 1966 request for the first full year of operation of the Division 
of Computer Research and Technology is $1,467,000, an increase of $531,000 
over 1965. 

Public Health Service 

Matioaal Institute of Gaoeral Medical Sciences 

List of Witnesses 

Dr, Frederick L. Stone, Director, National Institute of 
General Medical Sciences 

accompanied by 

Dro James A. Shannon^ Director, National Institutes of Haaltk 
Owen W. Scott, Executive Officer, National Institute of 

General Medical Sciences 
Donald E« Beaushamp, Budget Officer, National Institute of 

General Medical Sciences 
B» J. Sadesky, Financial Management Officer, National 

Institutes of Health 

Dr^ Luther L* Terry, Surgeon General 
Harry L. Doren, Chief Finance Officer 

Jasaes Fe Kelly, Department Comptroller 

Statement of Director, National Institute of General Medical Sciences, 

Public Health Service 
"National Institute of General Medical Sciences ' 

Mr. Chairman and Members of the Committee: 

This occasion marks my first appearance before the Committee as 
Director of the National Institute of General Medical Sciences. It is a 
privilege to discuss with the Committee those research and training pro- 
grams which fall within this newly established Institute. 

The progress of the Institute to date after two years fully justifies 
the importance the Congress has attached to the support of basic research. 
In creating this Institute, Congress demonstrated belief in the premise that 
basic research supplies the understanding and insight, the tools and method- 
ology for applied research. This reservoir of knowledge must be continually 
renewed and replenished to maintain the research momentum in biomedicine 
achieved by this Nation in recent years. 

Virus-Enzyme Relationships 

For many years scientists have been exploring fundamental life pro- 
cesses in simple biological systems such as bacterial viruses, which lend 
themselves to controlled laboratory study. These agents grow only within 
bacteria, which they invade in much the same way as do viruses that infect 
human cells . 

At the Albert Einstein College of Medicine in New York, a group of 
distinguished investigators has recently reported the discovery and purifi- 

cation of an enzyme essential for the reproduction of an infective bacterial 
virus, thus opening the way for possible future development of chemical 
virus inhibitors. 

Enzymes are biological catalysts that make it possible for life-con- 
trolling reactions to occur at rapid rates. The enzyme discovered by the 
Albert Einstein investigators was found in bacteria infected by viruses in 
which ribonucleic acid (RNA) is the genetic material. They have recovered 
the enzyme from cell-free extracts of these bacteria and have for the first 
time purified and characterized it sufficiently to demonstrate that it can 
indeed catalyze the formation of copies of the original viral RNA and that 
it is clearly different from known enzymes of the uninfected bacteria. 

The significance of this study is that the enz3raie can be extracted and 
studied outside its host, and the search can begin for a chemical inhibitor 
of the RNA type of viral infection. 

This interesting exploration in molecular biology, an exciting frontier 
of science, opens new opportunities for learning more about viruses and how 
to interrupt their cycle of multiplication, perhaps ultimately for man's 
benefit. The study is jointly supported by the National Institute of 
General Medical Sciences and the National Science Foundation. 


Virtually the entire evolution of anesthesiology as a scientific disci- 
pline has taken place in the past decade. This continues to be an area of 
special need which is beginning to feel the impact of new knowledge con- 
tributed through studies supported by this Institute's research and 
training programs. 

PromlTient among the studies conducted by one of the leaders in this 
field, Dr. Emanuel Papper of New York's Columbia University, is a project 


concerning the effects of anesthetics and other central depressants on 
spinal reflexes. Work to date by Dr. Papper and his associates suggests 
that the primary site of action of these drugs is in the brain stem rather 
than the spinal cord. This knowledge represents an important advance toward 
understanding the mechanisms of anesthetic effects on neuro-physiological 

Another outstanding research group is the team headed by Dr. Robert 
D. Dripps at the University of Pennsylvania. One of their recent findings 
is that deliberate lowering of the blood pressure can do a great deal to 
minimize blood loss during surgery. In some cases, blood pressure need not 
be maintained at a stable level, but may be varied according to surgical 
requirements . 

Experimental Pathology 

A gradual transition and new emphasis is taking place in research in 
experimental pathology. Through the use of electron microscopy and the 
tools and concepts of biochemistry, immunology, physiology and biophysics, 
new insight into alterations at the cell and tissue level is clarifying 
disease mechanisms. 

Dr. Kurt Benirschke at Dartmouth is using the armadillo to study 
developmental abnormalities. This animal is uniquely suitable for com- 
parative studies with the human fetus because of its developmental charac- 
teristics and drug sensitivity. I'Jhen given thalidomide, the animals aborted 
or produced malformed offspring, and in one instance a placental malignancy. 
The spontaneous occurrence of this cancer has beee previously reported 
only in humans . 

Burn Tnerapy and Wound Healing 

The death toll from severe burns continues at an extremely high level 

despite much work on the problem. The antibiotic control of infection, and 
other recent therapeutic improvements, has altered burn mortality little 
over the past several years. One new approach under investigation by 
Dr. Melvin Spira at Baylor University is immersion therapy in a silicone 

Research on wound healing has brought about advances stemming from 
biochemical and physiological studies. Search for a simple, efficient, and 
economical method of tissue repair has led Dr. John E. Healey, Jr., at the 
University of Texas, to use a liquid plastic adhesive instead of stitches 
in a variety of tissues. Experimental subject for this study is the dog. 

Disorders of Genetic Origin 

A unique opportunity to study the genetic history of a culturally 
isolated American group, the Old Order Amish, in Pennsylvania, has produced 
information on hereditary abnormalities which, through exact records, can be 
traced back to the 18th century. Dr. V. A. McKusick of the John Hopkins 
University has documented 49 cases of a disorder which has been named the 
Ellis-van Creveld Syndrome. 

A recessive gene causes a rare type of dwarfism in which adults reach 
a height of between 40 and 60 inches. An extra finger on each hand and 
serious malformation of the heart are also found. The syndrome first ap- 
peared after four or five generations of second and third cousin inter- 

Groups such as the Pennsylvania Amish are becoming increasingly rare 
in today's world and constitute an unparalleled human genetic resource. 
The high degree of cultural isolation and voluminous family records of these 
people present an opportunity to shed new light on disease patterns, on 
consequences of kinship and marriage systems, and on the biological con- 
sequences of inbreeding. 

Nex; Hormone from Sheep Glands 

A new hormone has been discovered during the past year in the course 
of a search for faster methods of isolating adrenocorticotropin (ACTH) from 
sheep pituitary glands. Dr. C. H. Li of the University of California, 
Berkeley, reports that this is the first hormone characterized chemically 
before its biological effects were studied and determined. 

The investigator has named the nev7 hormone lipotropin. The substance 
metabolizes fats both in the animals from which it has been recovered and in 
the test tube. It is not a growth-stimulant, nor does it stimulate the thy- 
roid or gonads. The effects of the nev7 hormone on human biological processes, 
including its potential for use against obesity and atherosclerosis, are 
being studied. 


The problems posed by long-term use of potent drugs common in present- 
day medical practice are only part of a complex challenge to scientists to 
understand and evaluate the effects of these and other chemj.cals vjhich have 
come into widespread use in our society. Even after years of trial and con- 
siderable evidence of their clinical benefits, no one knows with absolute 
certainty the long-range effects on people of common drugs such as the anti- 
biotics, anticoagulants, and hormones. The same is true of pesticides with 
respect to chronic exposure over long periods. Fundamental knowledge lags 
far behind practical application, yet only from fundamental studies will come 
the understanding needed for rational control. 

To attack this problem the National Institutes of Health has set up a 
coordinating unit within the National Institute of General Medical Sciences 
to reassess those research and training programs in the broad area identified 
as pharmacology- toxicology and to mount a coordinated national program. 

Four methods of support contribute to this over-all approach to the 


1. University-based Complexes or Centers of Research and Research 
Training . Broad and multidisciplinary studies will be directed toward the 
solution of problems which arise from the ever-present chemicals to which 
modern man is continuously exposed, both deliberately and inadvertently. 

Located at institutions of sufficient stature to have a profound 
impact on the phari^aco logy- toxicology field, the centers will provide ready 
access to clinical material and would have adequate resources of experi- 
mental animals. The development of scientific manpower in ph^rniaco logy- 
toxicology as a national resource will be a major objective of the 
centers program. 

At least four university-based centers can be foreseen in F.Y. 1966 
as potential candidates for the initiation of the proposed program. The 
development of such complexes would require a minimum of $1 million in the 
first year. 

2. Research Contracts (collaborative studies ). Some research problems 
are ideally suited to support through contracts. The harmful as well as 
beneficial ways in which biological systems are affected by chemicals must 

be determined, and obversely, the effect of biological systems on the chemi- 
cals themselves. Current knowledge has already indicated specific tasks 
which can be accomplished by contract. 

3. The Research Associate Program (intramural training activities ) , 
A plan to train about 10 research associates at the National Institutes of 
Health in 1966, as an extension of present intramural programs in pharma- 
cology-toxicology, is also proposed. Additional fellows will be added to 
the program in the following two years. This resource will represent a sub- 
stantial expansion of trained scientists with special competencies in 
pharmaco logy- toxico logy . 


4. Scientific Information — Communications Systems . A scientific and 
drug information communications program is planned as a major component of 
the total pharmacology-toxicology effort. Primarily, this segment of the 
program is the responsibility of the Division of Research Facilities and 
Resources. Other constituents «3f the Department of Health, Education, 
and Welfare are also contributing to the over-all communications program 
in this field. 


No single aspect of a national program for the support of the health 
sciences is more important than the training of promising young people for 
careers in these sciences. This crucial activity is the key to continuing 
excellence and productivity in research. The graduate training programs of 
this Institute, concentrated in the biomedical disciplines, are responsive 
to the need for sophisticated, in-depth training for scientific careers. 

The necessity for periodic regrouping and combining of research disci- 
plines now is mandatory if full advantage is to be taken of the exciting study 
opportunities afforded by advanced instrumentation and precision techniques 
which only a few years ago were unknown. These phenomena are changing the 
requirements of scientific training, and are being taken into account in the 
Institute's training programs. 

Training areas in this Institute which are particularly illustrative 
of a multidisciplinary approach are pharmacology-toxicology, molecular biology, 
the biophysical sciences, biomathematics, biomedical engineering and the 
behavioral sciences. 

Through its training grants programs covering about 20 research disci- 
plines, the Institute supports more than 7,000 trainees, two-thirds of whom 
are predoctoral candidates. 


This program constitutes the principal effort of the National Institutes 
of Health to support the training of carefully selected scholars for biomed- 
ical research in all appropriate basic disciplines. Thus, its impact is broad 
and its significance in the development of manpower for the nation in the 
basic health field is obvious. 

Research Fellowships 

The research fellowship program of the Institute, focused on indi- 
viduals rather than on programs, supports the training of as many young, able 
students as possible in anticipation of future research needs. This program 
concentrates on the basic biomedical disciplines and is therefore relevant 
to the entire research effort of the National Institutes of Health, 

In the years 1959-1963, this Institute supported approximately 500 
individuals who have received Ph.D. degrees in the medical and health- 
related sciences. In addition about 1,000 man-years of post-doctoral 
training were given. 

To meet the urgent need for training more young scientists. Congress 
appropriated an additional $1,800,000 in 1965 for predoctoral fellowships. 
This sum allows 300 additional young scientists to continue their studies 
in health -related fields. More than 85 percent of fellows, upon receiving 
graduate degrees, do research and most of them will become the teachers of 
coming generations of young scientists. 


In conclusion, Mr. Chairman, the request for the National Institute of 
General Medical Sciences for 1966 is $122,338,000, which will provide for the 
following increases: $2,827,000 in research grants; $2,239,000 in fellow- 
ships; $1,393,000 in training grants; $1,400,000 in collaborative studies; 

$136,000 in training activities; $164,000 in review and approval; and 
$30,000 for over-all planning, direction and coordination of the programs 
of this Institute. 

Public Health Service 
Biologies Standards 

List of Witnesses 

Dr. Roderick Murray, Director, Division of Biologies Standards 
accompanied by 

Dr. James A- Shannon, Director, National Institutes of Health 
George A. Brust, Executive Officer, Division of Biologies 

Mrs. Elisabeth Grubbs, Budget Officer, Division of Biologies 

B. J. Sadesky, Financial Management Officer, National 
Institutes of Health 


Dr. Luther L. Terry, Surgeon General | 

Harry L. Doren, Chief Finance Officer P 

James F. Kelly, Department 6omptroller 



Statemt^nt by DireciioCj Division uf Biologies Standards 

Public Health Service 

■Biologies Standards" 

Function of the Division 

The Division's primary function is to administer thoso provisions of 
tho Public Health Service Act pertaining to the safety, purity, and pott-ncy 
of biological products often referred to as biologies. Many of these products 
are derived principally from pathogenic microorganisms, and th> preparation 
requires careful control. 

Experience shown that such control can be accomplished most 
effectively within the context of an active research program. Thus, the 
programs of the Division are product-oriented; their scope, direction, and 
intensity are dictated by the need to provide essential information for tht- 
development of requirements and regulations for new products, as well as 
for the continuous improvement of tests to ensure the safety, purity, and 
potency of existing products. 

Implementation of F unction 

Control measures are based on a system of licensure. Following 
determination by the Division that the prescribed standards for safety, 
purity, and potency have been met, licenses for the manufacturing establish- 
ment and for the product are issued by the Department of Health, Education, 
and Welfare upon rccoirimendation of the Surgeon General. As of December 1, 
1964, 212 establishment licenses and 1,343 product licenses were in effect, 
the latter covering 291 specific products. 

The standards prescribed by the Division for the production and testing 
of biological products are set forth in regulations vhich are continually 
reviewed for adequacy. As scientific knowledge advances, revisions may be 
made. Once a product is licensed, continuing surveillance is maintained by 
periodic inspection of the manufacturers' facilities and production methods, 
review of records of production and testing, and by the testing of repre- 
sentative samples of products in the Division's laboratories. 

During fiscal year 1964, 9,149 Control tests were carried out to ensure 
the safety, potency, and purity of licensed biological prodiicts. These tests 
served as a basis for the release of 4,439 lots of products submitted by 
manufacturers during this period. The skills of trained professional 
personnel are required to carry out the many procedures involved, ranging 
from relatively simple sterility tests to complex and costly potency 
determinations and safety tests. 

Since most biological products cannot be standardized by chemical or 
physical means, their potency must be tested in relation to established 
reference preparations. To establish uniformity of potency, the Division 
provides standard or reference preparations to establishments engaged in 
biologies standardization. The development of these standards depends on 
intimate knowledge of advances in immunology, biology, virology, biochem- 
istry, and medicine. Of major consideration are improvement of methods of 
preservation and storage, such as freezing and drying, so that potency is 
maintained; selection or development of preparations which yield clear-cut 
endpoints in the control testing performed by manufacturers; and correlation, 
where possible, with standards established in other countries or with 
international standards. This year, the Division distributed 5,972 standard 


or reference preparations to coramercial establishments, health departments, 
universities, and research organizations. Included were 383 antitoxins, 
1,836 serums, 2,297 vaccines, 323 toxins, and 1,133 bacterial cultures. 

Research to provide basic data oh the properties of reference prepara- 
tions and to maintain their continuing stability is being carried out. 

The older, established products such as yellow fever, smallpox, and 
typhus vaccines, as always, demand attention. Smallpox, for example, 
continues to be an important health problem in much of the world. It will 
be a threat to smallpox- free countries like the United States until it is 
eradicated from endemic areas. This requires that the Division maintain a 
continuing program of research and control to ensure potent and stable 
vaccines. A recent study by the Division on the use of combined vaccines 
(smallpox, measles, and yellow fever) administered by the jet injector indicates 
the possibility of rapid immunization of large population groups when necessary. 

The following selected topics of current interest serve to illustrate the 
scope and nature of the work conducted by the Division. 

Measles and German Measles 

The licensing in 1963 of both killed and live virus vaccines for 
protection against measles (rubeola) has made possible the control of this 
disease. These vaccines are now widely used and have been shown to be most 
effective in preventing measles. 

The development of a vaccine against German measles (rubella) caused by 
the rubella virus, is now under study. 

Since 1940, the relationship between rubella infection during pregnancy 
and the development of congenital anomalies has been cause for concern. 



Since October 1962, investigators have been working toward the develop- 
ment of a rubella vaccine. This will take time, as evidenced by the six 
years of research from isolation of the measles virus to development of 
measles vaccine. The Division has, nonetheless, established an active 
research program to facilitate the control testing and ultimate licensing of 
a vaccine against rubella. 

The initial problem of propagating the virus has been partially solved, 
but problems in virus production, testing, and evaluation remain. Division 
virologists are working on these problems as they apply to safety and potency 
standards. One is the search for an experimental animal system to serve as 
a model for the study of human infection v/ith rubella virus. Another is the 
relationship of antibody formation to the prevention of congenital anomalies 
as well as to protection against the disease itself. A third is the develop- 
ment of an immunologic test of greater sensitivity and utility. 

Cholera Vaccines 

Although cholera vaccines have been used for more than half a century, 
precise knowledge of their protective power for man has been lacking. 
Renewed international interest has resulted in studies to establish the 
actual effectiveness of cholera vaccines in a number of areas where cholera 
is endemic. The Division is keeping in close touch with these investigations 
and is cooperating by performing laboratory tests on the vaccines in use. 
Until such information is available the Division cannot establish a realistic 
laboratory standard of potency that relates to human protection. 
Oncogenic Factors in Relation to Vaccines 

Many if not all mammalian and avian species harbor latent viruses, 
some of which may have a tumor-producing or oncogenic potential. These 

findings are of iuportance in biologies control since rriost virus vaccines 
are produced in narnmalian or chick enbryo tissue cultures or in enbryonated 

Representative of research conducted by the Division in this area is 
that on simian virus 40 (SV-40) . This adventitious virus, nov7 excluded fron 
vaccines, is notably different from the aany other simian viruses found in 
association with rhesus kidney cell cultures, for under certain conditions 
SV-40 produces tumors when injected into newborn hamsters. Since this 
contaminant represents a potential threat to the safety of all viral vaccines 
prepared in rhesus kidney cell systems, Division scientists promptly undertook 
an extensive program of research on SV-40 to examine its properties and to 
evaluate its importance to public health. This program is continuing. 

Using the same test system that was used for SV-40, it has now been 
shown by a number of workers that some of the adenoviruses, responsible 
for some common respiratory ailments, also have an oncogenic potential. 
The relation of these findings, if any, to human illnesses is not clear, 
and a great deal of research will be required for clarification. Implicated 
thus far, in addition to simian virus 40 (SV-40), are adenoviruses type 3, 
7, 12, 18, and 31. The time at which tumors develop in baby hamsters may be 
from 3 to 18 months, and depends on the virus and its concentration. 

A number of other viruses which may be encountered in vaccine production 
are known to have oncogenic properties. One is the virus of fowl leukosis. 
Steps have been taken to ensure that live virus vaccines produced in chick 
embryo tissue culture are free of this virus. 

There is also at present inadequate information concerning the possible 
oncogenic effect of vaccine preservatives, container materials, and adjuvants. 

particularly oil adjuvants which have been studied experimentally with 
influenza vaccine. 

The value of these studies is obvious for the entire field of cancer 
research; however, specific infornation is needed on aspects which concern 
vaccine safety. When the oncogenic virus is a contaminant of the vaccine 
it can, with considerable research effort, be eliminated by changing 
production techniques. However, if the vaccine virus itself has an oncogenic 
potential, the problem is infinitely more complex. It takes months and 
years and broad studies involving large numbers of animals to demonstrate 
the effects. 

Enforcement Activities 

Investigations of criminal violations of the provisions of the Public 
Health Service Act that apply to biological products have increased. The 
first prosecution and conviction under this Act involved false labeling 
and illegal shipments of human plasma. The second concerned a blood bank, 
wherein the bank and one of three individuals responsible were found 
guilty of false labeling; the conviction is being appealed. Another blood 
bank has been indicted for similar violations. 

The Division also cooperated with the Food and Drug Administration in 
investigations to secure information on the disputed anti-cancer preparation, 

Investigations of a similar nature may be a recurring obligation 
for the Division. Since this calls for detailed collection of information 
for legal use, a group has been designated within the Division to collect 
such evidence. 


Investigational New Drugs 

The Division has in the past kept itself informed of the results of 
clinical and laboratory studies of biological products in the developmental 
stages prior to the initiation of application for a license. Regulations 
which became effective in 1963 now require that persons engaged in clinical 
investigations of biological products must submit a "notice of claimed 
investigational exemption for a new drug" to the Division. As of June 30, 
1964, 95 such submissions had been made to the Division. 

Program Plans 

Mention was made of some of the work being done with a number of viruses 
which have oncogenic properties. Although the significance of such findings 
in relation to human disease is unknown, the very existence of this problem 
requires that it be thoroughly studied from the point of view of the safety 
of vaccines made from such viruses or from related viruses. This problem, 
which will involve a search for new test models and the examination of 
vaccine viruses and other components of vaccines within the use of existing 
models, is of such magnitude that its resolution can best be approached by 
enlisting additional scientific assistance. This could be accomplished in 
part through the mechanism of research contracts placed with organizations 
capable of this type of investigation. 

Recently, it has been increasingly clear that advantages for the 
Division's program are to be derived from an activity with full-time respon- 
sibility for the collection and dissemination of scientific and technical 
information pertaining to the control of biological products. The Division, 
as a leader in the field of biologies control, proposes to establish such a 
group in 1966. 

The workload associated with investigations of infractions of the 
pertinent laws and regulations has been increasing in the last fevj years. 
These investigations and the resulting follow-up actions show signs of 
remaining a continuing responsibility of the Division. The detailed work 
necessary to continue these investigations, as distinguished from the 
regularly conducted inspections, is extremely tirae- consuming. The Division 
will, of necessity, need additional staff devoted exclusively to this 
work during the coming fiscal year. 

The review of the "claimed investigational exemption" filings is also 
proving to be tine-consuming and detailed, with some of the filings 
required by the drug amendments of 1962 comprising thousands of pages of 
information. In order to keep abreast of the work and to increase its 
effectiveness we must strengthen this program. 

The Division considers it necessary to expand some of its control 
functions, particularly in the areas of the maintenance and development 
of standard preparations as well as investigation of the toxicological 
implications of biological products. With the proposed use of new 
adjuvants and other devices for the enhancement of the antigenicity of 
immunizing agents by a number of investigators and manufacturers, it is 
imperative that the Division study such preparations thoroughly before 
they reach the market for general use. 

In conclusion, the request for the Division of Biologies Standards 
is $6,406,000 for 1966 compared with an operating level of $4,959,000 in 
1965, or an increase of $1,447,000. 

Public Health Ser-^'ise 

National Institute of Child Health aiad Bsman Bevelopmeat 

List of Witnesses 

Dr. Doaald Harting, Acting Director, Hational Institute of 
Child Health aad Human Development 

Accompanied by 

Dr. jmsiBB A» Shannon, Director, Hational Institutes of laalch 
Dr. Joseph Bobbitt, Assistant Director, National Institute of 

Child Health and Human Bevelopaeat 
Calvin B. Baldmn, Executive Officer, S^tlonal Institute of 

Child Health and Human Development 
Gerald Atchison, Budget Officer, National Institute of Child 

Health and Human Developssent ^ 

B. J. Sadesky, Financial Managesisnt Officer, National | | 

Iiistitutes of Health i 

Dr. Luther L. Terry, Surgeon General 
Harry L. Doran, Chief Finance Officer 


James F. Kelly, !}@partment Comptroller 

Statement of Acting Director, National Institute of Child Health 
and Human Development, Public Health Service 

"National Institute of Child Health and Human Development" 

Mr. Chairman, and Members of the Committee: 

It is a pleasure to appear before this Committee, to report on 
the progress made by the National Institute of Child Health and Human 
Development during the second year of its life, and to touch briefly 
on its plans for the coming year. To carry out these plans, we are 
submitting a request for $53,524,000, which is $10,837,000 over the 
1965 budget. 

The Institute's aim is to help create knowledge which will help 
man to achieve his birthright to a normal, healthy life throughout the 
years, from conception to his last days. 

The accelerated progress toward this goal which the Institute is 
able to report is the direct result of action taken by the Committee 
last year in making certain we received the number of positions and 
the balanced funding needed to continue the orderly expansion of our 
activities in 1965. 

With the very important additional resources appropriated in 
1965, the Institute has undertaken appropriate expansion of its activities 
in high-priority programs, such as reproductive biology, aging, and 
mental retardation. One specific index of our increased activity last 
year is the fact that this past November, our Council reviewed 395 

applications, as against 233 applications reviewed at the same time 
last year, an increase of almost 70 percent. 

Both the productivity of Institute- supported research and training 
activities and the increased demand for support of these activities 
have been kept in mind in developing the 1966 budget. 

Reduction of Premature Birth 

One of the Institute's goals is a drastic reduction in the incidence 
of premature birth. Born before he is fully prepared for life on his own, 
the premature infant wages an uphill battle for survival and normal 
health, handicapped by incomplete development of many of his vital 
organ systems. He is particularly prone to serious respiratory difficul- 
ties, such as hyaline membrane disease. He is also more likely to have 
brain damage, mental retardation, and other disorders. And even when 
the premature infant survives undamaged, it takes a long time for him 
to catch up with his full- term counterparts. 

At the present time, approximately 7 of every 100 births in this 
country are premature--a rate that rises to better than 20 of every 100 
among the disadvantaged. Yet the causes of prematurity are still poorly 
understood. One of the major concerns of the Institute is the search 
for the causes and prevention of prematurity, for it seems clear that 
prevention of premature birth alone would reduce the incidence of many 
disorders and prevent many infant deaths. Additional emphasis will be 
placed on the problem of hyaline membrane disease, and the Institute 
expects that means of reducing this disease as a major cause of mortality 
of the newborn will be found. 


In the area of training, the Institute's support will contribute 
to the objective of having more scientists working in several of the 
developmental sciences. These include, for example, experimental embry- 
ology, developmental psychology, and developmental pharmacology. We 
also plan to support training opportunities in leading universities 
where developmental scientists of the future will be trained both in 
the basic sciences tindergirding the study of development and to achieve 
clinical competence in such fields as pediatrics, obstetrics, or internal 
medicine. In addition, we plan to establish fetal medicine, including 
prenatal diagnosis, therapy, and prophylaxis as a new biomedical discipline. 

Program of Direct Research 

We have begun the development of a strong and effective program 
of direct research, thus increasing the Institute's own competence to 
deal directly with the problems of child health and human development. 
In this past year, the Institute has made some progress in this area by 
acquiring a small direct research facility in St. Petersburg, Florida, 
now being used primarily by the Institute's Aging Program. An out- 
patient diagnostic and study unit for the Institute's Mental Retardation 
Program has been developed in cooperation with the National Naval 
Medical Center. We are developing a direct research program for the 
study of reproductive biology. This will be heavily oriented towards 
research relationships with investigators in Latin America, and will be 
based in Puerto Rico. 

In charting the Institute's course, we have been greatly helped 
by our Interdisciplinary Conference program. At each of the 22 conferences 

held during the first half of 1965, outstanding scientists worked with 
Institute staff in defining, conceptualizing, and developing research 
areas of critical interest to the Institute. 

Research Accomplishments 

Turning now to a very brief discussion of some of the Institute's 
accomplishments this past year, the number of research grants in the 
Reproductive Biology Program has almost doubled. This program now includes 
24 percent of the research and training grants being supported by the 
Institute and approximately 22 percent of research grant funds are budgeted 
for this program. Investigators supported by the Institute are exploring 
various aspects of ovarian function, testicular function, and the 
immunological aspects of reproduction. The use of subhuman primates 
is becoming increasingly important in the study of many basic problems 
relating to reproduction. Research and training to better understand 
the interrelationships between population growth rates and many aspects 
of human health and welfare is receiving an ever increasing amount of 
support from the Institute. 

The Institute's Perinatal Biology Program is particularly important. 
This stage in the physiology of reproduction presents many problems — 
spontaneous abortion, congenital malformations, premature birth, and 
much fetal wastage — along with other health problems. 

In the past year. Institute- supported grantees have advanced 
considerably in developing an understanding of a number of problems 
in perinatal biology. Some of the chief advances to date have been 
in the promotion of general measures which could spell the difference 
between the survival or death of the premature infant who also has the 
respiratory distress syndrome. 


By far the greatest advance of this type has been the work 
which now permits us to understand the processes by which heat is 
exchanged between a newborn infant and his environment. It is now 
apparent that the infant may require a close control of the thermal 
conditions which include not only the temperature, humidity, and air- 
currents around him, but probably--and more importantly — the temperature 
of surfaces which may radiate heat to him or accept heat from him by 
radiation. Studies supported by the Institute have shown that increased 
survival of small premature infants can be achieved by the provision 
of such radiant heat. 

In other activities concerned with the perinatal period, the 
Institute supported a conference in the field of intra-uterine surgery. 
The conference brought out the fact that intra-uterine surgical 
techniques can be applied successfully to safeguard the survival of 
a fetus who might otherwise die before birth, or emerge in a camr.ged 
state. Finally, the most important task faced by those who for 
premature infants is to provide enough oxygen to meet the infant's 
needs, and yet to restrict it sufficiently to prevent the blindness 
which in the past had been caused by the over use of oxygen. In order 
to provide objectivity in determining how much oxygen to give a pre- 
mature infant, arrangements are now being made for the design and 
development of a miniature monitoring device which will tell exactly 
how much oxygen actually reaches the body tissues. 

The Aging Program 

At the other end of the life-span, primary emphasis within the 
Institute's Aging Program is being given to increasing the number of 


persons trained to work on gerontological problems. Thus one recently 
awarded grant to the University of Chicago is being used to train 
researchers in adult development and aging. A number of trainees in 
this program are specializing in the social and psychological problems 
of middle age and old age. They are trying to find the answers to such 
questions as: "What are the life patterns of successful middle-aged 
persons?" and "What events lead middle-aged men to perceive themselves 
as burning out in their career and family roles?" 

Many of the research grants supported by the Institute's Aging 
Program are concerned with the study of progressive changes in cells, 
tissues, organ systems, and whole organisms. In one such research 
grant, investigators at the Masonic Research Laboratory in Utica, New 
York, are exploring the "error hypothesis" which is concerned with 
the aging of cells. The hypothesis states that, with continual use, 
some of the DNA molecules in the nucleus of the cell sustain damage 
and produce faulty messenger RNA which, in turn, results in production 
of defective or ineffective enzymes. 

The investigators have shown so far that liver cells from old 
rats, compared with those from young rats, produce more ribonucleic 
acid and protein. This finding may be surprising, if one thinks of 
the aging organism as being less active throughout. But within the 
"error" hypothesis, it makes sense. As errors accumulate, the cells 
become increasingly vulnerable to metabolic failure and die. 

Mental Retardation Program 

The Institute's Mental Retardation Program, one of four Institute 
programs that are concerned with specific developmental problems, is 
able to report considerable progress in increasing the potential effective- 



ness of our national resources in the fight against mental retarda- 

Working with the Division of Research Facilities and Resources , 
the Institute has helped plan broad programs of research in mental 
retardation to be conducted in two Mental Retardation Research Centers. 
These are located at the Albert Einstein Collge of Medicine in Yeshiva 
University in New York, and at the University of Washington School of 
Medicine in Seattle. 

In addition, much progress has been made in research by investi- 
gators supported by the Institute, For example, an investigator at 
the University of Wisconsin Medical School found that by feeding newborn 
macaques (a species of short- tailed monkeys) with whole milk formula 
containing excessive amounts of certain amino acids, genetically- 
determined inborn errors of metabolism could be induced and duplicated 
biochemically. These include phenylketonuria, histidinuria, hyper- 
glycemia, and maple syrup urine disease. 

The solid accomplishments which the Institute has been able 
to achieve this year are certainly every bit as much as we could have 
optimistically predicted 2 years ago when the Institute first reported 
to you. 

Grant supported investigators have reported advances which show 
promise of decreasing the incidence of maldevelopment and of increasing 
the quality of human life In the years to come. We have aided in 
the development of two large mental retardation centers; we have started 
our own direct research operation in St, Petersburg, Florida; and, we 


have made plans for other direct research activities at the National 
Naval Medical Center and in Puerto Rico, 

Our plans for next year are exciting. If our report last year 
may be considered a "tooling-up" report, and our report this year a 
"pilot operation" report, our report next year will reflect progress 
made by an Institute which has both a firmly based extramural research 
grant and training program, and an established program of research of 
Its own. 

Next year we expect to place a great deal of emphasis on 
longitudinal studies, and on developing our research efforts to learn 
more about how human beings learn. Our direct research operations will 
be expanded considerably. 

For these activities, Mr. Chairman, we are submitting a 
request for $53,524,000. This compares with a base of $42,687,000 for 
1965. The budget represents an increase over the 1965 operational 
budget of $10,837,000, For grants we are requesting an additional 
$9,319,000; of which $7,319,000 is for research and $2 million la for 
fellowships and training. For direct operations, we are requesting an 
additional $1,518,000, of which $280,000 will be used for direct research, 
$1,000,000 for collaborative studies, $30,000 for direct training 
activites, $107,000 for review and approval and $101,000 for program 

Public lealth Service 
National Cancer Institute 

List of Witnesses 

Dr. Kenneth M. Endicott, Director, National Cancer Institute 

accompanied by 

Dr. James A. Shannon, Director, National Institutes of Health 
Robert E. Learmouth, Executive Officer, National Cancer 

Fred V. Shaw, Budget Officer, National Cancer Institute 
B. Je Sadesky, Financial Management Officer, National 

Institutes of Health 

Dr. Luther L. Terry, Surgeon Geaeral 
Marry L. Doran, Chief Finance Officer 

Jasaes F. Kelly, Department Co!3^>troller fl 


Statement by the Director, National Cancer Institute 
Public Health Service 


"National Cancer Institute" 

Mr. Chairman and members of the Committee: 

During the past year we have continued to reshape Institute programs 
to meet new developments. Some modifications such as the special virus- 
leukemia program are apparent from the budget; others, such as the changing 
chemotherapy program, though less visible, are as significant. 

The additional fvinds appropriated by the Congress for the special 
virus- leukemia program have allowed us to greatly accelerate oxjr research. 
We speedily developed a plan and chart of the program, reviewed it in 
depth with our advisory groups, and promptly began its implementation. 
Much needed work is now under way, according to plan. 

The work on cancer causation is also moving along well. The impres- 
sive research developments on the role of DKA and KM. in heredity and 
control of the nature and functions of body cells are now beginning to 
be applied to the problem of how cancer-causing agents actually modify 
these cell control systems to produce cancer. 

The cancer chemotherapy program, already substantially reoriented, 
will be further modified as improved feedback information is obtained 
from the clinic, especially as we continue to improve the statistical 
reporting systems and increase the clinical pharmacology efforts. 

In addition, the steady progress in many fields continues and 
provides information so important for determining the directions to be 
taken by the scientists of the country and by the Institute in the future. 

- 2 - 

Much of the reorientation vas "based on the intensive program 
reviews completed by the Institute and with its major advisory groups 
during the past year. 

Virus- Leultemia Research 

I would first like to report on progress under the special appro- 
priation of $10 million initiated and appropriated by the Congress for 
the fiscal year I965 for additional research on virus and leukemia and 
related diseases. 

I immediately established a science/management team within my office 
to formulate a comprehensive overall program plan covering the four major 
areas of research: l) the cause and prevention of human leukemia; 2) the 
treatment of human leul?:emla; 3) "the natiore of animal leul^emias and their 
possible relationships to man; and k) the hazards in virus-cancer research 
and the problem of containment. A new program planning technique for bio- 
medical research, developed by my program planning staff, was used. Should 
the Committee have time, we would be pleased to go into detail. The research 
objectives were established for each of the four major areas; the various 
types of research efforts required to achieve these objectives were 
described; a determination was made of the types and levels of resources 
(in terms of people, facilities, material and equipment, and funds) required 
to perform the work; and, finally, all of these elements were Integrated 
both in content and in time Into a series of high priority research and 
operational flows which provide for optimizing performance and overall 

- 3 - 

Specific key talents from within the Institute, other federal 
agencies, and universities were mobilized into eight working groups who 
have been actively developing detailed research plans for each of the 
four areas of study. In addition, the chairmen of each of these groups, 
who are senior Institute scientists, also meet each month to discuss the 
overall program and to serve as a focal point for the continuous monitoring 
of program progress. 

The plan now involves more than 150 projects representing both ex- 
pansions of research efforts already in progress and entirely new research 
efforts. Tte flexibility of the plan is maintained by continuous updating 
based on information from the program; necessary modifications are made as 
required. The bulk of the work is being performed under Public Health 
Service contracts, although some of it may be conducted under grants, and 
some is already under way in the laboratories and clinics of the National 
Cancer Institute in Bethesda. 

Investigation into the cause and prevention of human leukemia is 
based on the assumption that at least one kind of virus is an indispensable 
element for the induction of at least one kind of human leukemia and that the 
virus continues present in the diseased individual. This is supportable 
from extensive information an hianan and animal leukemia. Integrated research 
and development Td.ll be directed toward the primary objective of prevention 
through an effective vaccine or other control methods of virology. 

In the treatment of leukemia, total kill of leukemic cells has been 
achieved in mice and approximated in a few patients. Slight ixnprovements 
in therapy may make this feasible in many patients. A major objective in 

- 1+ - 

this program area is therefore the conrplete destruction of all leuliemia 
cells with minimal toxicity for the patient. Research will be directed 
not only toward better new driogs and better use of drugs now available, 
but also toward better support of the patient by amelioration of drug side 

Information from a variety of sources suggests the importance of 
investigating the relationship between the occurrence of leukemia in persons 
who have associated with domesticated animals ancT the occurrence of leukemia 
in these animals, Leukemias in certain animals will be studied for evidence 
of viral etiology and their antigenic and other relationships to human leulcemia. 

The control and containment of biohazards is a newly recognized 
problem in cancer research. Only recently has it become apparent that 
certain viruses, heretofore thought to be species- specific, can in some 
cases cross species lines, especially in the highly concentrated preparations 
(in some cases thousands of times beyond the normal state) required for 
laboratory experiments. This constitutes a definite hazard to personnel 
engaged in virus studies and to the success of their research should the 
materials with which they are working become contaminated. Additional 
measures for the control of these biohazards are therefore urgently needed 
and are being instituted and further studied under the special virus-cancer- 
leukemia program. 

Recommended Programs 
Advisory body review of National Cancer Institute programs produced 
two specific recommendations which the Institute is proceeding to carry out. 

- 5 - 
One concerns determination of cancer risks of agents introduced into lajrge 
population groups. The other pertains to biohazards in cancer research, 
already mentioned in connection vith the special virus- leukemia program. 

Determination of possible cancer risks of such agents as pesticides, 
certain contraceptive agents, industrial chemicals, etc., introduced in 
variety under changing conditions into population groups which themselves 
may be changing and -vridely distributed geographically constitutes one of 
the most important and most difficult areas of cancer investigation. More- 
over, the latent induction period for human cancers apparently extends over 
several years, probably at least a decade for most types of cancer. Studies 
in this area therefore are difficult to plan and conduct. Following a 
meeting of experts on cancer, gynecology, contraception, reproductive 
biology, pharmacology, and epidemiology, the Institute has initiated plans 
for a feasibility study directed toward the possibility of a full scale 
study of certain hormonal agents. Design and implementation experience 
gained in this study will be valuable for dealing with other agents of 
possible cancer risk. 

Hazardous and potentially hazardous materials, both viruses and 
other agents such as chemicals and radiation, singly and in combination, 
must be dealt with in ongoing studies, but as advances are made, we must 
further improve facilities, equipment and procedures to insure safety to 
personnel and materials. In conjunction with the Special Virus- Leukemia 
Program, but also as part of the carcinogenesis efforts, the Institute is 
erecting temporary hazard facilities on the NIH groxinds, involving special 
containment space and equipment and backed up by a research and development 

. 6 . 
contract to design, mock up, test, fabricate and monitor new units and 
devices for protection of man and experinents. These facilities are 
critically importaLnt from two standpoints: first, personnel working with 
hazardous and potentially hazardous materials must be able to perform 
experiments in laboratories which provide the maximum protection afforded 
by the current state-of-the-art in containment; and second, unconventional 
laboratory facilities are needed which will provide the flexibility required 
to evaluate, under actual laboratory situations, the procedures, techniques, 
and equipnent resulting from the research and development efforts in bio- 
hazards containment and control performed under contract. As experience 
and knowledge is gained in these studies, information will be provided to 
other institutions conducting hazardous work as an aid to their planning, 
particularly as regards facilities and equipment needs. 

Chemotherapy Program 
One of the difficulties in the management of the chemotherapy program, 
which is now ten years old, has been the lack of certain inforaiation from 
the clinical evaluation of drugs necessary to further improve our drug 
evaluation procedures. Since we have not always been able to obtain this 
information from the cooperative programs in medical schools and other 
hospitals, the Institute is developing a clinical pharmacology program 
that is closely integrated with extensive, in-depth pharmacology and toxi- 
cology investigations of new agents. A imit of the program is being estab- 
lished at the Baltimore Public Health Service Hospital in which National 
Cancer Institute and Johns Hopkins University Medical School staff 

- 7 - 
scientists will participate. Additional pharmacology, biochemistry and 
toxicology work with industrial participation, will be integrated into the 
program at this unit. 

Advisory groups have recommended that the clinical activities in 
Collaborative Research be enlarged beyond chemotherapy to include other 
aspects of cancer treatment. Program responsibility for development of the 
various methods of treatment, and for the establishment and coordination of 
appropriate combined therapeutic methods, will be placed in a Caxicer Therapy 
Evaluation Center that will parallel the Cancer Cliemotherapy National Service 
Center under the Associate Director for Collaborative Research. Also, improved 
reporting of clinical evaluation of therapy is being achieved by a central 
statistical office which is coordinating data received from the 23 study 
groups representing about 250 hospitals cooperating in clinical trials under 
highly developed protocols. 

New Task Forces 
The excellent progress made by the Acute Leukemia Task Force has 
encoiiraged us to malte this kind of approach in other areas. In the hope of 
getting maximum results from the coordination of laboratory and clinical work, 
and the development of models for research, three new task forces are being 
activated. One of these groups will give intensive study to malignant lymphoma, 
including Hodgkin's Disease. Another will deal with chronic leuliemia and 
multiple myeloma. A third will devote itself to cancer of the breast, 
utilizing hormonal and non-hormonal agents in combination therapy. 

New Carcinogenesis Program 
Under a contract with the Chicago Medical School, scientists of the 
school's Division of Oncology under the direction of Dr. Phillipe Shubik will 

- 8 - 
conduct an integrated program of testing and research on the increasing 
number and complexity of environmental contaminants, operating on a contin- 
uous, long-term basis with flexibility to solve problems as they arise. 
The carcinogenic effects of chemicals such as pharmacological agents, 
combustion products, food additives, and industrial materials will be tested 
in animals over prolonged periods. Studies will be made of the mechanisms 
of carcinogenesis, that is, how the chemicals are metabolized, what products 
are formed, and how they interact with cells and tissues to produce malignancy. 

With the establishment of the Chicago Medical School project financed 
at $1,095,768, we now have three major laboratory groups developing a joint 
plan of carcinogenesis research. The other two are the Oak Ridge National 
Laboratory project conducted jointly x^ith the Atomic Energy Commission, and 
our in-house group at the National Cancer Institute. 

Cell Biology 
This Committee asked that we explore additional program mechanisms 
through which fundamental biological research can be brought to bear in 
the cancer area. I am submitting a special report on a survey of investi- 
gators in the field concerning the needs and resources required. 

Appropriation Bequest 
I^ir. Chairman, the request for the National Cancer Institute for 1966 
is $1^9,968,000, compared to the I965 operating level of $lii8,67^,000. The 
1966 budget request provides for increases over I965 as follows: $3, 52i)-,O00 
for research grants; $613,000 for research fellowships; and $Ti)-9,000 for 
direct research. The budget request also reflects a decrease of $1, 8l6,000 
in training grants and $1,928,000 in Collaborative Studies. Other smaller 
increases and decreases are described in the budget justification. 

Public Health Service 
National Institute of Mental Health 

List of Witnesses 

BTc Stanley F. Yolles, Director, National Institute of 
Hental Health 

accompanied by 

Dr. Janes A. Shannon, Director, Hatienal Institutes of Haalth 
Dr. Rayoond Feldman, Acting Deputy Director, Matioaal 

Institute of Mental Health 
George M. Kingman, Acting Executive Officer, National 

Institute of Mental Health 
B. J» Sadesky, Financial Management Officer, national 

Institutes of Health 

Dr. Luther L. Terry, Surgeon general 
Harry L. Doran, Chief Finance Officer 

Jm^s F. Kelly, Departoent Comptroller 




Stateitffint of Director, National Institute of Mental Health 
Public Health Service 


"National Institute of Mental Health" 

Mr. Chairman and Memhers of the Committee: 

It is a pleasure to appear before this Committee as the Director 
of the National Institute of Mental Health to report to you on the 
current statvis and projected requirensents of the national mental health 

All of VLB at the Institute are working to establish a nationwide 
system for prevention of illness and delivery of services embodying the 
highest q^lality of care through improved training of personnel and the 
rapid dissemination and application of new research findings. Total 
mental health services are to be available and accessible to persons in 
need in their own communities, I should like today to sunmsarlze, in the 
light of our experiences dxiring recent months, how the Institute plans 
to meet that goal. 

In essence we are working to: develop a constellation of community- 
based services for all who need themj construct coimmmity mental hesilth 
centersi continue otir laboratory and field researches into the causes, 
treatment, and prevention of the mental ilJjiessesj translate results of 
that research into services that help people; relate mental health plan- 
ning to all other community planning so as to achieve mentally healthy 
community environments; and train skilled nanpower in the core mental 
health professions and the non-professional service areas. 



At the inception of the program, our first task was to assist the 
States in their efforts to formulate long-range, interagency plans to 
meet the people's mental health needs. Comprehensive planning began in 
1963 when Congress appropriated $k.2 million as the Federal government's 
share in financing the States* planning program. 

A like sum was appropriated for I96U. It is now obvious that 
there was a widely felt need for mental health planning. This is 
evidenced by the response from States, local governments, and professional 
and citizen's groups. 

At least 25,000 professionals and other leading citizens have taken 
an active part in the planning endeavor in some manner as volunteers. 
In at least 22 States, the Gtovemors have participated personally in 
this planning. More them 32 States have already made provisions affecting 
budgets and administrative reorganization so that mental health planning 
can be continued beyond the period of Federal support as an agency of 
State government. 

It wovild seem that comprehensive mental heedth planning is on its 
way toward achieving that portion of the program goal assigned to it. 

Hospital Improvement and Inservlce Training 
Congress, having made the planning program possible, then 
appropriated funds to improve immediately the treatment of patients in 
State mentsG. hospitals and institutions for the mentally retarded. Funds 
were also provided to finance on-the-job training of non-professional 

hospital personnel. 

These events were exceedingly iraportant, for it will take time to 
in5)lement the connnunity centers program, and patients \rtio are currently 
resident in mental hospitals cannot and shoxild not wait for the quality 
of treatment which is the right of any human being in this country. 

The Hospital Improvement Program, as we have called it, has been 
enthusiastically received by the hospitals. By the end of 1965> 
approximately 155 public institutions caring either for the mentally ill 
or the mentally retarded will be demonstrating treatment improvement 
projects. This represents 36 percent of the total nTimber of such 
institutions in the country. 

The program of Inservice Training Grants, through -vrtiich hospital 
personnel can upgrade their skills, is also progressing satisfactorily. 
About 20,000 attendants, aides emd houseparents will have received this 
training in the first year of grant svtpport. This will not only pix)vide 
additional skilled non-professionckLs in mental hospitals; it will also 
increase the non-professional manpower pool for community mental health 
centers. This training program, therefore, benefits the hospital patient 
today and will benefit the center patient tomorrow. 

In summary, these facets of the Institute program indicate that — 
while the community centers construction program is being established — 
the States are well along in their planning efforts; the treatment pro- 
vided hospiteil patients is improving; hospital service personnel is 
becoming uKsre skilled; and community services are expanding. 


This is all to the good. I should like now to discuss our 
program for producing an adequate supply of mental manpower. 


It is today quite clear that only with vigorous and continued 
growth of training can the Nation meet its mental health manpower needs. 

With your sitpport, the Institute has been able to initiate, 
sustain and expand a nationwide training program that both responds to 
and stimulates the entire CGmqprehensive mental heeilth program. 

The annual nuniber of gradxiate NIMH stipends awarded has increased 
from 219 in 19^ to more than 7,000 in 19614^. Over this period, the 
Institute has svipported the training of approximately 23,000 psychia- 
trists, psychologists, social workers and nurses. In addition, six 
thousand physicians in general practice have taken postgraduate courses 
in psychiatry and thousands of medical students have received some 
training in this medical specialty. 

In addition, the Institute supports research training in the mental 
health aspects of psychology and the biological and social sciences. 

The current computation of manpower requirements projected by the 
Institute for I97O indicates that by then we will need 87,000 profession- 
als in the four core disciplines of menteuL hesGLth. This is double the 
^44,000 professionals ^o were available in I960, and will make possible 
the deployment of as many as 23,000 professionals to coimminity mental health 
centers, while allowing for growth in the supply of individuals working 
in other menteG. health settings. It will also be necessary to train an 

adequate supply of such professionals as occupational therapists and 
rehabilitation counsellors. 

The clergy, teachers, lawyers, law-enforcement officers and 
physicians in general practice-even though their primary concerns 
exist outside the mental health field — often are the first to establish 
contact with persons needing mental h^lth consultation. The Institute 
continues to support specialized training so that these professionals 
can deal swiftly and judiciously with situations relating to mental 

Because of the continued interest of the Congress in supporting 
training efforts, training centers of quality and stability have been 
developed. These centers are prepared to expand their training efforts. 

In this vital period, when historic developments in mental health 
are evolving, the groiandwork has been laid for the production of man- 
power trained to cope with increasing responsibilities. The opportvinlty 
for continued expansion is apparent. With such growth, we can achieve 
the manpower goals of the national mental health program. 


Despite our involvement in all other parts of the national mental 
health program, the foundation of the Institute's overall mission--the 
inprovement of the mental health of the people of the United States — 
continues to be the quest for new knowledge. 

The paths of research are intricate. Clues to the cause, prevention 
and treatment of the mental illnesses are being sought in body chemistry; 

in the mechanisms throxigh vhich the "brain functions; in the environ- 
mental factors that create stress; in the effects of psychoactive 
drtigs; in the efficacies of other modes of treatment. 

The contribution of the biochemist has implications for the 
pharmacologist; the findings of the anthropologist are relevant to 
the social psychologist. Often, a single research team is composed of 
individuals representing many diverse disciplines in hiiman knowledge. 

It will be absolutely impossible for me today, Mr. Chairman, in 
this short time to do more than s\iggest to you the implications of the 
vast and fascinating range of investigations in \4iich the Institute 
research progrsun is involved. But I can assure you that the continued 
support of these research efforts is vital. 

President Johnson, in his State of the IMion message, said, "Our 
goal is to match the achievements of our medicine with the afflictions 
of our people." The goal of ovo: Institute research investigators is to 
provide American medicine with the knowledge on which to base such an 

Take, for example, the mental disorder schizophrenia, which is 
still a scientific enigma. A number of investigators are making 
progress in understanding the biological basis of the disordered 
processes involved. Some are engaged in biochemical studies in which 
functional behavior disturbances are seen as an expression of a general 
metabolic disorder. Others see schizophrenia as traceable both to stress 
and to action by a specific brain center. 


A crucial part of the Institute research program continues to 
be study of the specific properties and modes of action of a variety 
of the psychoactive drugs in widespread clinical use, as well as 
evaluation of the effects of new drugs. Findings in this area lend 
strong support to the feasibility of treating acute psychoses in a 
variety of settings, rather than solely in mental hospitals, since 
drug therapy can suppress severely disturbed or disorganized behavior. 

As research in a3J. the mental illnesses continues, the Institute 
adapts findings of the Laboratory to field demonstrations, and goes 
on to incorporate new methods of care, treatment and rehabilitation 
into everyday clinical practice and service programs to help mentally 
disturbed people. 

With the explosion of new knowledge, it is also necessary to 
assemble research findings and disseminate them :ri.dely. The National 
Clearinghouse for Mental Health Information has been created vd.thin the 
Institute to collect and store infonnation on a worldwide basis, and 
to make it readily available to all v/ho have need for it. 

The Institute's activity in special problem areas such as 
alcoholism, drug abuse, and crime and delinquency continues« 

As indicated by the consistent increase in requests from individuals 
to the WLME for information, and because of our need for more knowledge 
of the subject, it is iuiperative that in I966 we increase our studies 
of alcoholism, both in the quantity and depth of research. 

Narcotic drug abuse is another problem of concern. In the past 
year. Institute investigators studying narcotic drug effects have found 

that the use of nalorphine as a narcotic antagonist can provide 
ambulatory treatment of the narcotic addict. Biey have also devised 
a method to determine clearly and rapidly whether patients are using 
or have used narcotic drugs. Any one of 30 narcotics can be extracted 
from urine, blood and body tissues, and procedures have been developed 
to identify these extracted narcotics. 

In the area of crime and delinquency control, the Institute 
continues to concentrate its research, demonstration projects, 
consviltation services and personnel training on juvenile delinquency. 

As I conclude this report, Mr. Chairman, I should like to comment 
that — like our knowledge of the atom, once thou^t to be a single 
system with few components — our oversinqplified view of human behavior 
has evolved into an awareness of complexity. 

The integrity of human adjustment requires the balance of many 
forces. The enigmas of mental health will never give way to less 
diversity of approach, less shrewdness of method, less precision of 
instrumentation, and less effort than have the secrets of the atom. 

The mission of the National Institute of Mental Heeilth must thus 
be seen as encompassing programs of variety, technical intricacy and 
scope extending well beyond the conventional present-day conception of 
mental health. 

With imaginative use of the new knowledge gained, the Institute 
can, in conjunction with the several States and local communities, provide 
for a broad array of preventive and treatn^nt services conveniently 
available to everyone in the Nation. 

TO conduct our progrsun, I am requesting $208,969,000 for I966, 
as compared with an expected operating level of $188,109,000 in I965. 
This is an increase of $20,860,000 which is spread among the activities 
of the Institute. The increase is discussed in detail in the budget 
justification. The request for I966 is distributed as follows: 

Grants ; 

Research „ $8U,T90,000 

Fellowships 8, 364,000 

Training 83,231,000 

State control programs 6,730,000 

Subtotal, grants 183,135*000 

Direct operations ; 

Research 11,560,000 

Collaborative studies 3,864,000 

Training activities 1,390,000 

Professional smd technical assistance, . , 4,657,000 

Review and approval of grants 3*499,000 

Program direction 864,000 

Subtotal, direct operations 25*834,000 

Total 1966 appropriation request 208,969,000 

Pssblie laal£fe Ser^ie© 
CoBststsetio^ of CoaiamiBity ^sital Isalth G©@tar@ 

List of Wit3©8S@s 

Dro Staaley Fe Yolles, Direetorj Matioaal Iastife©6e ®f 
Mental Health 

aecompaaied by 

Dr« Jaaaes A, Shaffinoa, Director, National Iiis£iti3t@a of l@alth 
Dr. R&fmowi Feld^Qj Aetiag D@p«ty Director, Matioaal lastitut© 
of Mental Health 

George K, Kiskgaasj Acting E^ee?ati^4'e Officer, Matioaal Iffistitut© 

3f Mental Health 
Be Js Sadesky, Fisiancial l^mageraent Offieerj Mstioaal lastitutes 

of Health 

Dr. Luther Lo Terry ^ Surgeon General 
Harry L» Dor®a» Chief Finance Officer 

Fe Kellys Departaent Cosaptroller 



Statement by Director, National Institute of Mental Hesath 

Public Health Service 


"Grants for Construction of Community Mental Health Centers" 

Mr. Chairman and Members of the Committee: 

When the Congress adopted the Community Mental Health Centers Con- 
struction Act in 1963, it did far a»re than authorize Federal grants to 
help finance the construction of buildings. 

It is now cleeir to aill that Public Law Q8-l6h can provide the 
foundation for the entire concept of comprehensive community -based mental 
health services, as well as the physical foundations of the mental health 
centers themselves. 

I should like to discuss, briefly, what has occurred in the past year 
to substantiate my statement. 

As you know, the Centers Act authorized the appropriation of $150 
million over three years to finance up to two -thirds of the construction 
costs of any one center whose sponsors could meet the terms and intent of 
the statute. The Act also required the Secretary of the Departanent of 
Health, Education, and Welfare to issue regulations under which construction 
grants could be awarded. 

The staff of the NationsQ. Institute of Mental Health submitted sug- 
gestions for those regulations, Mr. Chairman, after exploring every 

available source of knowledge and experience. We did this so that the 
regiilations could be adapted to the mental health planning in each State, 
and tailored to the mental health needs of each community, while meeting 
the requirements of the Centers Act. 

These regulations have been adopted and promulgated, and extensive 
efforts have been made to assure that States understand their provisions. 
Any bold new approach to a problem results in new problems. To resolve 
them in each instance calls forth a diversity of approaches. But I c£in 
confidently report to you that with your support we are prepared to ac- 
celerate the construction of centers and, therefore, to hasten the day 
when mentally ill persons can be treated in their home communities, and 
the mental heaO-th of those communities ceui be improved. 

State Plans 

Under the regulations pertaining to the Centers Act, each State is 
required to submit a State Plan for Community Mental Health Centers. This 
plan includes an inventory of existing resources, a sxirvey of the needs of 
the area and the establishment of priorities to meet those needs. This 
is necessary because each State needs to know what it has before it can 
plan additional resources that depend upon already existing services. 

The State Plan also takes into account other pleuining efforts. The 
mental health center will be designed to mesh with plsins for medical 
facilities, mental retardation facilities, planning in mass transportation, 
crime and delinquency control, and in other special problem areas, such 

as alcoholism. Each State Plsm for Centers, accordingly, will be a com- 
prehensive plan. 

Following approval of the State plan, communities in that State will 
submit applications to the State agency responsible for the centers program. 
If the application conforms to the approved plan, it will be assigned a 
priority and forwarded to the Public Heeilth Service for final review and 
approvELl . 

Essential Services 

When a State accepts an application for a center, its sponsors must 
be prepared to provide at least a minimum of five essential mental health 
services: inpatient, outpatient, partial hospitalization and emergency 
services for treatnent of the mentally ill, and educational and con- 
sultative services to individuals, groups and agencies in the commiunity 
concerned with prevention of mental illness and improving the environment 
of 6ill its residents. 

A few centers now provide these services, but the concept of the 
national community -based mental health program goes further. In addition 
to providing this constellation of available services, the proposed 
program must further assure that patients, menteil heSLlth professionals, 
and clinical information csui move from one type of service to another — 
within the center — without difficulty, so that treatment will be tailored 
to the needs of the patient, rather than to the heretofore prevalent ap- 
proach of separation of services. 

The regulations also require sponsors to treat all who need that 
treaianent, so long as they live in the connnunity the mental health center 
is designed to serve. 

The regulations, of course, spell out details, mschanics and criteria 
both for the program and the requirements of construction. As I have said, 
we face many problems, since American coramunities have a wide variety of 
customs, political and administrative stnictures, and fvtnding patterns. 
Nonetheless, today the States and localities, with conscious design, are 
establishing mental health services which are accessible, available, 
coordinated, prevention-oriented, and capable of coping with ajiy form of 
mental illness 

The Congress has appropriated the first $35 million for construction 
grsmts, to be awarded in fiscal 19^5 and available through 1966. A 
significant n\amber of centers built with Federal assistance should be in 
operation by I968. 

State Allotments 

All of the States last fall were informed of the amount of their 
allotments under the first year's appropriation. But since these funds 
are not actually obligated until the final part of an application has 
been approved, the process of utilizing those allotments taJces about 
12 months. 

Because no center application can be considered until the State plan 
is approved, and. because planning efforts by most States are extensive. 

it will "be the middle of this calendar year before we receive any laarge 
number of State plans and subsequent center applications. 

So you can see, Mr. Chairman, that we are still very early in this 
program, but I am delighted to be able to tell you that already about kO 
States have indicated their eagerness to particijiate in the centers program 
and upwards of 100 communities have plans to submit applications for centers. 
In fact, there is such enthusiasm in some States that their agencies expect 
to submit State plaxis and applications at the same time. 

Interest in the program has proved to be far ranging. We have had 
many hundreds of inquiries from individual citizens, from commxmity groups, 
from professional organizations, and from Congressmen. The professional 
organizations in meetings with our staff have all indicated their enthusiastic 
support, as have the State and Territorial Mental Health Authorities who 
met here in Washington just a few weeks ago. 

With the appropriation of the $50 million authorized for the second 
yeax of the program, we shoiild be well on our way toward establishing 
between 5OO and 700 centers by 1970. 

The projections are, of coxrrse, based on the availability of trained 
manpower and on the ability of the center sponsors to secure adequate 
financing for operation of the centers following construction. 

We have found in a n\Jmber of conferences across the country, Mr. 
Chairman, that in many communities — perhaps in most of them -- there is 
a pressing and urgent need for services. President Johnson emphasized 

this point in his ^alth Message to the Congress when he said, "Facilities 
alone cannot assure seirvices." 

Staffing Assistance 

As a resxilt of his recommendation, a bill has been introduced in the 
Congress calling for the provision of staffing assistance for those new 
services added in community mental centers that provide the essential 
elements of service. 

Such assistance would do much toward helping conammity centers become 
established and toward eliminating at least a portion of the initieuL financial 
burden. In this way, each center would be allowed time to develop permanent, 
stable methods of financing its operations. 

Insurance Coverage 

Other important factors in financing men^fcal health seinrices will be 
private contributions, payment of fees by patients, and expanded health 
insurance . 

In this latter area, an Institute task force on insurance, following 
consultation with representatives of prepayment and other health insurance 
plans and with labor and managen^nt groups, recommended minimal specifica- 
tions to improve and broaden insurance coverage of both inpatient and out- 
patient treatment of mental illness. 

The contracts negotiated in 196!+ in the major autonrabile and agricultural 
implement industries include insursuice providing substemtial coveraige for 

partial hospitalization and outpatient care for psychiatric illness. These 
contracts increase insurance benefits for some two million employees and 
their dependents, and mark a major brestkthrough in this area. 

Recent results eire encouraging and, as coverage increases, more patients 
in community mental health centers will he able to pay for a larger portion 
of the cost of treatment. At this time, however, since health insurance 
for all illness pays only approximately 25 percent of the total medical 
bill, and a far lesser proportion of the mental illness bill, the significance 
of insurance coverage in its relation to community mental health services 
should not be overrated. 

Still, its implications are among many meemingful advances, which give 
us confidence that the conraunity -based mental health program will operate 
to change the traditional pattern of custodial, long-term care of nental 
patients in isolated institutions. 

The need for this change became manifest in 1962. The Congress acted 
in 1963. The components and mechanics of a community program were established 
in 1964. The fran^work of the program has been well defined. However great 
the problems, the promise of the program is greater. The manifest need 
has become a challenge to be met by local. State, and Federal cooperation 
in the years ahead. 

Public Health Service 
National Heart Institute 

List o£ Witnesses 

Dr. Ralph E. Knutti, Director, National Heart Institute 

accompanied by 

Dr. James A. Shannon, Director, National Institutes o£ Health 
E. E. Henschel, Executive Officer, National Heart Institute 
John Reeder, Budget Officer, National Heart Institute 
B. J. Sadesky, Financial Management Officer, National 
Institutes of Health 

Dr. Luther L. Terry, Surgeon General 

Harry L. Boram, Chief Finance Officer 

James F. Kelly, Department Comptroller 


Statement by Director, National Heart Institute 
Public Health Service 


"National Heart Institute" 

Mr. Chairman and Members of the Committee t 

It has been past practice to introduce this statement with statistics 
describing the heavy toll in death and disability exacted annually by the 
cardiovascular diseases. Since these will be covered elsewhere, I will merely 
point out that the research assault on this family of disorders has reduced 
mortality rates from all major cardiovascular diseases except coronary heart 
disease. That these declining death rates have not always been reflected by 
reductions in total deaths is due to our rapid population growth. 

The most spectacular research gains have been registered against 
infectious heart diseases, hypertension, congenital heart disease, and rhexnnatic 
heart disease. But even the two greatest killers, stroke and arteriosclerotic 
heart disease, are beginning to show signs of yielding a bit to the Incessant 
research pressure. The overall death rate from strokes has declined somewhat. 
Death rates from arteriosclerotic heart disease, though still increasing among 
some segments of the population, have declined among women under 53; and, among 
white males aged 45-64, death rates appeared to level off during 1960. 

Heart Institute Research 
The research program conducted and supported by the National Heart Institute 
blends basic research into the structure, function, and abnormalities of the 
cardiovascular system with applied research aimed more directly at the solution of 
specific clinical problems posed by the cardiovascular diseases. During 1964, 
nearly 2500 cardiovascular research projects were pursued at NHI, at universities 

and hospitals throughout this country, and in research Institutions in a number of 
foreign countries. Results of these projects appeared in more than 3,000 scientific 
papers and abstracts published during the year. The following summaries represent 
only a very small sampling of those results. 

Atherosclerosis and Coronary Heart Disease . Elevated blood levels of certain 
fatty substances (lipids) have been found to be the factor most consistently 
associated with Increased susceptibility to atherosclerosis. While elevated blood 
cholesterol has continued to be the prime suspect, growing evidence indicates that 
elevated blood levels of neutral fat (hypertriglyceridemia) may also substantially 
Increase heart-disease risk. Modest elevations of plasma triglycerides are fairly 
common among Americans; and, at present, relatively little is known about the causes 
of this phenomenon and its clinical significance in the development of coronary 
heart disease; and even less is known about dietary manipulation or other measures 
for combatting this potentially Important clinical problem. 

Studies currently underway at NHI Indicate that the problem of hypertriglycer- 
idemia is more conqjlicated than previously supposed^ Formerly, only two types had 
been recognized: one type induced or made worse by diets high in fat, the other 
induced or made worse by diets high in carbohydrate. The NHI studies Indicate that 
"mixed" hypertriglyceridemias (Induced or made worse by dietary fat and carbohydrate) 
are probably far more common than either. Some hypertriglyceridemias are made 
worse by "lipid lowering" formula diets high In polyunsaturated fats, but respond 
favorably to diets high in fats of normal composition. This suggests that dietary 
regimens designed primarily to reduce blood cholesterol should also be studied for 
their effects on triglyceride levels. A diet that produced sustained triglyceride 
elevations while it lowered cholesterol might be a mixed blessing at best. 

Clinical studies by NHI grantees have shown that nethallde plus nitroglycerine 
greatly Increased the amount of exercise that subjects with angina pectoris could 

perform before the onset of chest pain. Exercise capacity after both drugs was 
2-5 times greater than that after nitroglycerine alone. By blocking beta receptors 
of the sympathetic nervous system, nethalide holds down the increases in heart 
rate and output normally elicited by exertion. This action keeps heart work at a 
level more commensurate with its limited blood supply. The study suggests that 
beta blocking agents may be valuable adjuncts to nitroglycerine and similar drugs 
in the clinical management of angina pectoris. 

A significant niamber of patients with heart disease develop irregularities 
of heart rhythm. Arrhythmias are a dreaded con^jlication of heart attacks, and they 
are also common in patients convalescing from cardiac surgery. While many arrhythmias 
may revert to normal spontaneously or can be corrected by drug therapy, others may 
progress to cardiac arrest and death. A new technique that appears highly effective 
in correcting arrhythmias is coupled pacing, in which paired electrical stimuli 
are delivered to the heart in rapid succession by a special pacemaker. These 
paired stimuli slow heart rate, normalize the heart's contraction sequence, and 
substantially increase the vigor of its contraction. Animal and clinical studies 
at NHI have shown that coupled pacing readily controls runaway heart rates, what- 
ever their cause, and also appears effective against other types of arrhythmias. 
The findings indicate that coupled pacing may be highly useful in the clinical 
management of arrhythmias, certain other forms of heart disease, and also in the 
postoperative care of patients undergoing cardiac surgery. 

NHI grantees report that exposing animals with Induced heart attacks to 
pure oxygen at a pressure of 3 atmospheres (hyperbaric oxygenation) during the first 
two hours protected them against heart arrhythmias, helped to sustain heart output 
and systemic blood pressure, and substantially increased survival. Mortality during 
the first 24 hours was only 29 percent in the animals receiving hyperbaric oxygen 
therapy, versus 92 percent in the control group. After one week, half the treated 

animals were still alive, whereas none of the controls had survived beyond the 
fourth day. Hyperbaric oxygenation has already proved valuable in conjtmction 
with surgery to correct congenital heart defects causing severe tissue oxygen 
deficiencies and in the treatment of hemorrhagic shock. This study suggests 
that it also holds promise in the treatment of heart attacks. 

Hypertension . The catechol amines norepinephrine and epinephrine are power- 
ful heart stimulants and blood vessel constrictors long suspected of playing an 
important role in essential hypertension. Thus, compounds which could inhibit the 
synthesis of these amines by the body might provide valuable new therapeutic agents 
and also valuable research probes to study blood-pressure control mechanisms and 
derangements in those mechanisms that might underlie hypertension. 

Earlier this year, NHI scientists isolated and purified the enzyme (L-tyrosine 
hydroxylase) that ultimately limits the rate of norepinephrine production by the 
various tissues of the body. Subsequently several inhibitors have been found, the 
most effective being L-alpha-methyl tyrosine (Merck Sharp & Dohme) . Animal studies 
by NHI scientists indicate that this agent is highly effective in blocking catechol- 
amine synthesis in vivo . Although it is still too early to tell whether this or 
other inhibitors of L-tyrosine hydroxylase will merit serious consideration as 
potential therapeutic agents against hypertension, they should be immensely 
valuable in future studies to clarify, and perhaps re-evaluate, the role of catechol 
amines in various facets of metabolism. 

The carotid sinus is a pressure-sensitive receptor (baroreceptor) that normally 
acts as a buffering mechanism to stabilize blood pressure at normal levels. Reacting 
to changes in carotid artery pressure, the carotid sinus initiates reflexes that 
tend to normalize blood pressure through appropriate changes in heart rate, heart 
output, and blood-vessel tone. The results of many studies have suggested that, 
during the development of hypertension, this and other baroreceptors become less 

sensitive to blood pressure increases. The increased "tolerance" of these receptors 

may then act to sustain the hypertension, whatever its original cause. 

NHI grantees have developed an implantable electronic device called a baropacer 
uhat compensates for decreased sensitivity of the carotid sinus in hypertension by 
delivering trains of electrical impulses to the carotid sinus area whenever changes 
in the heart's electrical activity herald an increase in systolic blood pressure. 
By Imitating the normal activity of the carotid sinus, these impulses elicit reflexes 
that stabilize blood pressure at normotensive levels. The device has effectively 
controlled blood pressure in dogs with induced hypertension, and it appears to cause 
none of the undesirable side effects that may attend drug therapy. 

Surgery . Today, the Starr-Edwards "ball-in-a-cage" valve is the prosthesis 
most widely used for replacing hopelessly damaged mitral or aortic valves. Although 
the valve is dependable and durable, the ball narrows the effective orifice to some 
extent and offers significant resistance to forward flow. NHI grantees have devised 
a new valve in which the ball is replaced by a meniscus-shaped disc of Teflon or 
Silastic that seats on a metal ring in the cage. During forward flow, the disc 
floats up and pivots to one side, increasing the effective orifice of the valve. 
This, together with the extreme lightness of the disc, reduces the resistance to 
forward bloodflow. Extensive tests in animals indicate that the new valve combines 
the desirable flow characteristics of leaflet or flap valves with the dependability 
and durability of ball valves. 

Currently undergoing trial in animals at NHI is a suction-operated, quart- 
sized heart- lung apparatus. If the device proves feasible, it may be the prototype 
of convenient, cheap, mass produced, and disposable heart-lung machines for open- 
heart surgery. The device has a very high oxygenating efficiency, eliminates the 
hazard of gas bubbles entering the blood through leaks in the membrane, can be 
sterilized in an autoclave before use, and requires very little blood for priming. 


The low priming volume would simplify blood procurement problems, reduce the risk 
of hepatitis and transfusion reactions, and reduce the cost of open-heart surgery. 

Many of the desirable features of the new heart- lung device have subsequently 
been incorporated in the design of a small, disposable artificial kidney with an 
efficiency double that of the best artificial kidneys currently in use. The volvmie 
of fluid required for effective dialysis is so small that it can be discarded after 
a single passage through the artificial kidney, eliminating th^ need for a re- 
circulation system and dialysate pump. The device operates on such a low perfusion 
pressure that no blood pump is needed. 

Although the device is barely off the drawing board, work thus far has pointed 
up a number of means by which the efficiency of artificial kidneys can be substantially 
improved. It further suggests the technical feasibility of cheap, disposable 
artificial kidneys that might be suitable for "at home" dialysis for victims of 
renal failure. 

Some Highlights of Program Progress 
Sponsored jointly by the National Heart Institute, the American Heart 
Association, and the Heart Disease Control Program, the Second National Conference 
on Cardiovascular Diseases brought together 700 of the nation's leading authorities 
on heart and circulatory disorders. The goals of the Conference were to summarize 
the current status of cardiovascular research, training, and community programs; to 
define specific areas of need; and to make recommendations concerning areas of 
special importance in expanding and intensifying the research effort against the 
cardiovascular diseases. The report of this conference, a document of nearly 
1400 pages, provides the most complete and authoritative summary yet compiled on 
progress, opportunities, and needs in the cardiovascular field. 

A co-operative study currently getting underway is concerned with the clinical 
evaluation of urokinase. This clot-dissolving agent appears highly promising against 

certain of the thromboembolic complications of atherosclerosis that are so often 
responsible for the crippling and lethal manifestations of the disease. At present, 
the drug is being tested against peripheral vascular thrombosis and pulmonary 
embolism; but the National Advisory Heart Council has recommended that the highest 
priority be allotted to broadening the project to encompass definitive studies on 
the effectiveness of urokinase against coronary thrombosis. 

Scheduled for completion during 1965 is the Diet and Heart Disease Feasibility 
Study begun in 1963. The findings of this study should be of great value in 
determining whether large-scale population studies are warranted to assess the 
effects of dietary modification on mortality from heart disease. 

A scientist with experience in the Framingham Study has been assigned to 
Hawaii to collaborate with medical groups there in developing a study of an unusual 

? experiment of opportunity. The pattern of mortality from coronary heart disease 
and cerebrovascular disease among persons of Japanese ancestry now living in 
Hawaii differs markedly from that found in Japan and that found in Caucasians 
living in Hawaii. Coronary heart disease causes nearly 3 times as many deaths 
among men of Japanese descent in Hawaii as in comparable aged men in Japan. This 

I increased rate is still less than half that found in men of this age in the U. S. 
population as a whole. This situation strongly suggests that the changes in 
patterns of living in Americans of Japanese descent is increasing their rate of 
development of coronary disease. The Heart Institute considers that this unusual 
circumstance deserves further investigation to isolate the factors most inqiortant 
in creating this changing pattern of disease. 

The architectural plans for the proposed Gerontology- Building have been 
approved and construction will begin this May. The four story structure, with 
about 210,000 square feet of floor space, will be the largest gerontological . 
research facility in the country. 


The National Heart Institute is formulating plans for a comprehensive, co- 
ordinated research and development contract program to supplement biomedical 
research currently underway on artificial hearts. Hopefully, an intensified 
research and development effort may make artificial hearts a clinical reality 
in the near future. 

Mr. Chairman, the request for the National Heart Institute is $131,612,000 
for 1966 as compared with the $124,824,000 appropriated in 1965. Of this amount, 
$113,457,000 will be allocated for extramural research and training activities 
as follows: $92,254,000 for research grants, $6,375,000 for fellowships, and 
$14,828,000 for training grants. The remaining $18,155,000 will be allocated 
for direct operations as follows: $12,187,000 for direct research, $2,881,000 
for collaborative studies, $261,000 for training, $2,358,000 for review and 
approval activities, and $468,000 for program direction. 

Public Health Service 
Natioaal lastitute of Deatal Research 

List of Witnesses 

Kr, Francis A» Arsold; Jr.^ Director^ Hstional lastitefias of 
Dental Research 

accompanied by 

Dr, Ja®es Ao Sfeanrs©!!, Direstor. Mational Institutes of Baalth 
Herbert C» Chrlstofsrson, SKecutive Officer^ national 
Institutes of Dental Research 

Mrse Frsaices H« Pettinato, Budget Officer, Hational lasJtltrate 

of Dental Research 
Bq J. Sadeskyj Finaasial Msnagaaient Officers National 

Institutes of Health 

Dr. Luther Le Terry, Surgeon General 
Harry L. Doran, Chief Finance Officer 

Jffiaes F. Kelly c Department Oonptroller 

Statement by Director, National Institute of Dental Research 

Public Health Service 
"National Institute of Dental Research" 

Mr. Chairman and Members of the Committee: 

This statement is made in behalf of the National Institute of 
Dental Research. The oral and dental structures are important to all 
of us. The mouth is the pathway through which we receive nourishment 
and the mechanism through which we speak. Deformity or injury to the 
face is perhaps the most dreaded of wounds. The patient with oral or 
facial cancer, the patient with cleft lip or palate, the patient with 
buck teeth, the patient with deformed chin bear testimony. 

The magnitude of the Nation's burden of oral diseases is a matter 
of record and is well known to the members of this Committee. Experi- 
ence has shown that the problems of oral disease cannot be met by 
improvements in treatment alone. The billion unfilled dental cavities, 
the millions of individuals who have lost their teeth because of perio- 
dontal disease, the large number of children bom each year with facial 
deformities, all attest to the critical need for the kind of dental 
research that will contribute new knowledge of oral disease mechanisms 
and their control. 

Considerations such as these have broadened the horizons of 
dental research. The Dental Institute has therefore recognized that 
responsibility for research in oral disease includes responsibility for 
the study in depth of the underlying causes for these diseases as well 
as study of methods of prevention and treatment. 

The Institute has a responsibility to study dental decay. Such 
research is based on fundamental studies of the broad and complex field 
of mineralization of tissues. The Institute has a responsibility to 
study periodontal disease, the gum disease x^hich afflicts to some degree 
our total adult population. These studies are based on fundamental in- 
vestigations into the molecular structure and chemistry of the connective 
tissues which are involved in periodontal disease. Similarly, the study 
of deformities of lip and palate has been extended into fundamental 
research areas of developmental biology, neuromuscular physiology and 

The past two decades have seen at least one major oral disease, 
dental caries, yield significantly to research, through the development 
and application of water fluoridation as a control measure. Today, 
in our Bethesda laboratories and in those of many universities, research 
has made appreciable progress toward a better understanding of the 
treatment, control, and ultimate prevention of oral disease. 

Dental Caries 

Tooth decay, one of the oldest diseases known to man, is the most 
prevalent disease in the United States. The Institute has been engaged 
throughout its 16-year history in studies directed at understanding what 
causes the decay of teeth, what can be done to treat such decay, and, 
most important of all, what can be done to prevent it. 

Studies in causation center around the factors of calcification, 
bacteria, nutrition, and heredity. Particularly significant are the 
caries investigations begun a few years ago and previously reported to 


this Comlnittee. These studies have demonstrated that decay in both 
hamsters and rats is a disease entity which develops only in the 
presence of specific bacteria. Our scientists have followed this 
finding with evidence that dental decay can be modified or eliminated 
in animals through suppression of the specific bacteria, changing the 
diet, and enhancing tooth resistance through such measures as fluoridation. 

A grantee at the National Children's Cardiac Hospital, Miami, has 
recently shown that strains of human cariogenic bacteria can establish 
the disease in the hamster, indicating that the streptococcus is 
probably a factor in decay in man. This finding has two important 
aspects: 1) It shows that caries in animals is basically similar to 
the disease in man; 2) It indicates that specific forms of therapy with 
appropriate medication can be designed. 

Studies in mineralization of tissues conducted in university 
laboratories, and supported by research grants, are giving noteworthy 
results. They are building a basic picture of the manner in which 
mineral crystals establish themselves and grow; how they ascume their 
particular shape in enamel; and how these processes are affected in the 
demineralization that results in caries. Such information is also of 
basic importance to a better understanding of periodontal disease. 

Fluoridation has been an area of continued interest and respon- 
sibility in dental research at the National Institutes of Health from 
its beginning. These endeavors have shown the beneficial effect of 
water fluoridation in the prevention of dental decay; they have estab- 
lished optimum levels of fluoridation; and recent research has demon- 
strated a possible mechanism through which the beneficial effect may 
be derived. Institute scientists have also shown that the effect of 
fluoride is not restricted to young children, but lasts into adult life. 

Periodontal Disease 

Periodontal disease is the major cause of loss of teeth in adult 
life. Researchers are attacking this problem from the point of view of 
proteirl metabolism, histochemistry of connective tissue, and the 
bacteria in the diseased mouth. Recent studies have shown that micro- 
bial and dietary factors definitely affect periodontal tissues, and 
further study is seeking to find out whether underlying changes also may 
result from specific enzyme action. While there is as yet no true 
definition of the enzyme pattern in periodontal disease, there has been 
progress this year in the identification in animals of enzyme changes 
in experimentally produced vitamin C deficiency disease commonly called 
scurvy. Many years ago this disease condition in humans was shown to 
be associated with severe periodontal involvement. These recent studies 
may give us a clue as to what factors in vitamin C deficiency are 
important in periodontal disease. 

Dental Institute biochemists have also contributed to a better 
understanding of the composition and structure of collagen, a protein 
important not only to oral tissues but to other tissue components of 
the body. Their studies indicate that the collagen molecule is com- 
posed of three polypeptide chains which form a rigid rod-like structure. 
As part of a progressive maturation process j covalent crosslinks form 
between adjacent molecules to form a cable-like structure having great 
stability and tensile strength. Interferences with formation of the 
crosslinks by toxic chemicals or their destruction by certain enzymes 
may be a factor in certain connective tissue disorders including 
periodontal disease. 

Grantees of the Dental Institute are making studies of the growth 
and development of transplanted or implanted teeth. Experimental tooth 

. .'^ .-■ 


transplants in monkeys have shown a characteristic immune response which 
produces rejection of the transplant. However, in both animals and 
humans, movement of a tooth fromi one point to another in the mouth of 
the same individual produces excellent chances of survival. At Brown 
University in Rhode Island, plastic teeth are being implanted in baboons, 
and apparently this produces less adverse reaction than transplanting 
teeth from another animal. Studies on implantation have implications 
beyond the mere replacement of teeth. The technique may provide new 
knowledge of the reactions of the periodontal tissues and thus add to 
our knowledge of periodontal disease. 

Oral Soft Tissue Diseases 

The relationship of the herpes simplex virus to the occurrence 
of "cold sores" or "fever blisters" in man has been demonstrated in a 
number of laboratories. Recently, however, scientists have identified 
six distinct strains of the virus by antigen-antibody tests, and have 
found that different strains of the same organism may be isolated from 
the same individual in different disease attacks. They have also found 
varying antibody protective mechanisms in the blood streams of these 
individuals . 

In another study, conducted in collaboration with the Division 
of Biologies Standards, causal relationship between canker sores and 
a transitional L-form of bacteria has been suggested. This unusual 
organism has been observed in the lesions and in the blood of patients, 
and it also produces experimental ulcerations in rabbits. 

Oral-facial Deformities 

The study of birth defects of the face, particularly cleft lip 
and palate, is a most important Institute responsibility. Grant funds 

are supporting investigations in many university centers with studies 
ranging from the causation of birth defects and their genetic origin 
to rehabilitation of the patient suffering from them. Some of the 
approaches, for obvious reasons, take long periods of time since 
evaluation of methods of therapy, growth patterns, and psychological 
and speech changes is usually slow. However, each year advances our 
ability to deal with this serious health problem, and the seven large 
multidisciplinary centers for cleft palate research are beginning to 
give us important baseline studies. 

There is evidence in animals that drugs taken during pregnancy 
can produce oral deformities. At the Dental Institute oral defects 
are produced in 100 per cent of white rats by the administration on 
specific days of gestation of an anti-nausea drug called meclizine 
hydrochloride. Through intricate research an Institute physiologist 
has determined that a particular chemical breakdown product is resp- 
ponsible for the deformities. 

Dental Materials 

Important new developments have occurred in the research on 
restorative and reparative materials used by dentists. Sponsored 
research, by contract and grants, is attempting to develop a filling 
material which will chemically or otherwise permanently bond to tooth 
structure. Significantly, for the first time a materials science depart- 
ment in a leading engineering school has, with grant support from the 
Dental Institute, elected to commit a major research effort to the 
development of improved dental and medical materials. A successful 
outcome of this field of study would literally revolutionize the 
practice of dentistry. 

Clinical Studies 

In the Institute's clinical investigations outstanding results 
have been achieved in the study of effects of high speed instrumenta- 
tion on the dental pulp. These studies have given to practicing 
dentists clear guidelines on specific technics of cavity preparation. 

The transfer this year of the Dental Department from the NIH 
Clinical Center to the Dental Institute has given the Institute a 
Dental Services Branch. This change is reflected in our budget and 
will be reflected in the greater opportunity for clinical research 
activity. Close working relations between research and practicing 
dental clinicians should prove helpful to patients and to our research 
potential . 

The research grants program currently provides 355 research 
grants extending to all 50 American dental schools and to some 75 other 
university environments. Last year a series of program-project grants 
was inaugurated at several universities covering multidisciplinary 
attacks upon specific basic problems in the dental field. This program 
has expanded this year, and accomplishments are impressive, as I have 
alteady indicated. 


A clearly felt problem in dental research is the scarcity of 
scientific manpower. Particularly in the basic, non-clinical sciences, 
additional numbers of well trained scientists are required, and training 
programs have therefore been established not only in clinical areas. 

but also in such fields as metallurgy, the chemistry of materials, 
biophysics, genetics, and speech pathology. 

The Institute budget now supports over 90 training programs 
in more than 60 institutions, providing training opportunities for 
some 460 potential research vi7orkers. In addition, there are 82 
fellowship students pursuing courses of study in research under 
Dental Institute sponsorship. 


The goals of research in all the oral disease entities are not 
Utopian. They are reasonably achievable in the not too distant future 
through the widened application of research effort. 

The request for the National Institute of Dental Research is 
$22,177,000 as compared with an operating level of $20,355,000 in 1965. 
The increase of $1,822,000 will provide an additional $1,399,000 for 
research, fellowships and training grants. The balance of $423,000 
will provide for strengthening research and program direction 
activities in our direct operations in Bethesda and for support of 
central services. 

Public Health Service 
National Institute of Arthritis and Metabolic Diseases 

List of Witnesses 

Dr. Don&ld G. Whedon, Director, National Institute of 
Arthritis and Metabolic Diseases 

accompanied by 

Dre James A. Sh&nnon, Director, National Institutes of Health 
Dr. Benjamin T. Burton, Associate Director, National Institute 

of Arthritis and Metabolic Diseases 
W. Gilbert Baylis, Executive Officer, National Institute of 

Arthritis and Metabolic Diseases 
Donald F. Brown, Budget Officer, National Institute of 

Arthritis and Metabolic Diseases 
B. J. Sadesky, Financial Management Officer, National 

Institutes of Health 

Dr. Luther L. Terry, Surgeon General 
Harry L. Doran, Chief Finance Officer 

Jai^s F. Kelly, Department Comptroller 


Statement by Director, National Institute of Arthritis and Metabolic Diseases 

Public Health Service 

"National Institute of Arthritis and Metabolic Diseases" 

Mr. Chairman and Members of the Committee; 

I am grateful for this opportunity to appear before you again to report 
on this past year's progress, and to assess the needs of the National Institute 
of Arthritis and Metabolic Diseases for the fiscal year 1966. 

Most of the diseases within the province of this Institute 'are not only 
chronic and disabling in nature, but also highly diverse and thus pose a 
mosaic of problems. Arthritis, diabetes and other metabolic diseases, and 
disorders of the blood, bone and liver, and of the gastrointestinal tract 
require for their solution comprehension of intricate and complex mechanisms. 
I would like to report to you just a few of the research findings which have 
yielded Information most critical to the understanding of these diseases. 

Arthritis and Rheumatic Diseases 

The concept that rhevmiatoid arthritis is the result of abnormal auto- 
immunity is the most widely held among current working hypotheses. There Is 
promise that a much greater understanding of autoimmune reactions will eventually 
uncover not only the nechanisms of rheumatoid arthritis but of a number of 
other connective tissue disorders as wella 

This past year Institute grantees strengthened the hypothesis that 
rheumatoid arthritis is the result of a hypersensitive response when they 
succeeded in transferring an experimental type of arthritis, which resembles 
rheumatoid arthritis in man, from ill experimental animals to healthy ones 
by injecting them with cells which play a key role in immunologic reactions. 

- 2 - 

In addition, two other groups of Institute grantees have provided further 
understanding of the complex reaction which causes joint inflammation and 
cartilage destruction and which appears to involve rheumatoid factor, an 
abnormiil protein fraction present in the blood of most persons with rheumatoid 
arthritis. Studies by the first group indicated that joint inflammation may 
be associated with the presence of certain rheumatoid factor-containing 
granules in the scavenging white blood cells found in the joint fluid of 
patients. Their studies suggested that complexes made up of gamma globulin 
and rheumatoid factor may appear in the rhevimatoid joint and that these deposits 
may be ingested by scavenging white blood cells drawn to it. 

The second group of Institute grantees found that ingestion of these 
rheumatoid factor deposits by white blood cells resulted in activation of 
certain tissue-eroding enzjnnes, which were recently implicated in the joint 
destruction associated with rheumatoid arthritiSa Evidence from these and 
other studies suggests that, following initiation of an inflammatory reaction 
in the joint lining, these enzymes are released from the white blood cells in 
which they lay dormant originally, gain access to the joint cartilage and 
chemically degrade it. 

Progressive cartilage destruction also characterizes osteoarthritis, or 
degenerative arthritis, the most common of the arthritic disorders. During 
the past year, an Institute- supported scientist showed that prolonged, large 
doses of salicylates, such as aspirin or related drugs, above and beyond their 
pain-killing effect, act to inhibit protein-digesting enzymes believed 
responsible for such cartilage degeneration. This finding suggests that 

- 3 - 
salicylates, in continuous and adequate dosages, may have prophylactic value 
in degenerative types of human arthritis. 

I reported to you last year on the results of a population study of 
rheumatoid arthritis conducted among North American Indians, the Blackfeet 
of Montana and the Pima of Arizona. This study by Institute scientists 
indicated that the frequency of rheumatoid arthritis was related neither 
to heredity nor to climate. Because of widespread interest in this study, 
I am pleased to report that- our Institute scientists are planning to pursue 
their Investigations of the natural history of rheumatoid arthritis by 
returning to the study areas to determine further its frequency, sex distri- 
bution and population selectivity. As a by-product, a concurrent preliminary 
study of diabetes among the Pima has revealed that this tribe has a much 
higher percentage of diabetic individuals than the general American population. 
This preliminary study may offer a new slant for research in diabetic disorders. 
A complete survey of these new potentials will be made during the coming year. 


The urgency of basic and clinical research in diabetes was underscored 
by a recent report from the Public Health Center for Health Statistics indica- 
ting that the number of Americans with diabetes may be four million. This 
staggering statistic is brightened only by the productive efforts of research 
scientists studying the possible basic causes of the disorder. 

The classic theory of the causation of diabetes has held that the disease 
is caused by impaired or absent generation of insulin by the pancreas. During 
recent years, investigations of Institute grantees, and others, have shown 
that this classic concept does not hold in all cases, especially in the type 
of diabetes characterized by a gradual onset during advanced age. Here it 

- 4 - 
has been demonstrated that the preceding and early stages of maturity onset 
diabetes, especially when associated with obesity, are characterised by an 
abnormally high secretion of insulin; the insulin present in the circulation, 
however, does not appear to be 1007o metabolically active in facilitating 
normal carbohydrate (sugar) utilization by the individual. It has been proposed, 
therefore, that specific substances destroy or Inactivate insulin after its 
release from the pancreas. 

This past year, the finding by Institute-supported scientists of an 
enzjmie that promotes the destruction of insulin has lent additional credence 
to that theory. This enz3nne, glutathione- insulin transhydrogenase. Is 
synthesized by the human liver. Grantee investigators, and Institute scientists 
in Bethesda independently, have sho^^m that this enzjmie cleaves the insulin 
molecule into two chainso Concurrently, another grantee scientist demonstrated 
that the separated "B" chain, when bound to albumin in the blood, acts as a 
natural antagonist of insulin in the circulation* 

The level of active insulin is strongly affected by the liver enzyme; 
when excessive amounts of the enzyme are produced, much insulin is destroyed 
directly, and insulin-antagonists are formed which tend to inactivate other 
insulin molecules which have escaped direct enzymatic attack. This work has 
not only raised the possibility that enzjmiatic destruction of insulin may 
play an important role in the etiology of diabetes j but has pointed to the 
importance of continued research to find a means of inhibiting the action of 
such enzymes. 

In investigations related to the use of the oral anti-diabetic drugs. 
Institute grantees have shown that phenformin effectively reduces the 
characteristicallj' exaggerated insulin response to glucose in diabetes. 
This suggests a possible prophylactic use for agents such as phenformin in 

- 5 - 
prediabetes. By suppressing the overstimulation of the pancreas in the pre- 
diabetic state, which may eventually lead to early pancreatic exhaustion, 
the judicious use of such drugs could conceivably delay the onset of overt 

In related studies, a new drug of the sulfonylurea group, acetohexamide, 
has been found by an Institute grantee to be a safe and effective oral drug 
for the treatment of maturity-onset diabetes. 

New Metabolic Disease 

A highly significant research finding last year prompted me to include 
in my oral testimony before the Subcommittee of the Committee on Appropria- 
tions of the Senate a last-minute report that the defect in a new metabolic 
disease characterized by mental retardation, homocystinuria, had been determinedo 
This finding was made by scientists from the Institute collaborating with in- 
vestigators from the National Institute of Mental Health. The NIH investigators 
have demonstrated that the absence or lack of activity of a specific enzyme, 
cystathionine synthetase, is the basic defect in this disease. Without this 
catalytic agent the body is unable to convert a naturally occurring amino 
acid, methionine, to another important amino acid, cysteine. Because this 
enzyme is missing, a child born with homocystinuria may suffer from a lack 
of sufficient cysteine just after birth, a time in life when the body's need 
for this amino acid is particularly high. Such a deficiency may be accentuated 
if the infant is fed cow's milk which, in contrast to human milk, is relatively 
poor in cysteine. This has led the Institute scientists to suggest that 
early cysteine supplementation of the diet of such infants may prevent or 
minimize otherwise irreversible damage. 

- 6 - 
Gastroenterology and Diseases of the Liver 

Disorders of the gastrointestinal system, which may range from stomach 
upset to peptic ulcer, are among the most frequent ills to afflict man, as 
Vi7ell as some of the least understood by scientists. For example, the cause 
of gastri c ulcers has long defied investigative efforts. This past year, 
however, an Institute-supported scientist has provided strong evidence that 
prolonged food stagnation in the stomach may cause gastric ulcera by prompting 
excess secretion of gastrin, the stomach hormone which stimulates secretion 
of corrosive gastric juices. Another group of Institute-supported scientists 
demonstrated this past year a unique method of treating ulcerative colitis. 
A ten-year trial of treating such patients with local corticosteroid drug 
therapy in the form of suppositories and retention enemas has shown that 
such procedures are superior to other methods of drug administration in 
improving the course of the disease. 


Endocrinology, the study of the internal glandular secretions of the 
body and the glands which discharge these secretions, is an area of biomedical 
research which has produced some startling findings during the past several 
years. One such finding was by an Institute grantee in Sweden who has induced 
ovulation successfully in previously sterile women by treating them with 
human gonadotropic hormones. These patients were enabled to have children; 
in fact, multiple births were quite common among them. 

Other noteworthy developments include a new diagnostic method which 
permits differentiation between primary and secondary aldosteronism (a disorder 
of the adrenal gland affecting salt metabolism) without recourse to exploratory 
surgery, and identification of a brain center, the hypothalamus, as a regulator 

- 7 - 
of growth hormone secretion, 

Urological Diseases 

In urology, relatively a new field of study for the Institute, several 
important advances which warrant continued investigation, have been made 
this past year. One such study involved treatment of total urinary Incontinence, 
the inability to control the natural evacuation of urine, which is a major 
medical problem which generally does not respond well to current surgical 
techniques. Institute grantees have now developed a new, effective operation, 
the results of which are encouraging enough to justify further use. During 
the past year other grantees showed that measurement of the enzyme lactic 
dehydrogenase proved to be a relatively simple and precise method of detecting 
various unsuspected kidney disorders in the general population. 

Basic Research 

Elucidation of the fundamental, physical, biochemical, and physiological 
facts which make up the basic fabric of all the biological and medical sciences 
is one of the prime activities of this Institute, Although gratifying progress 
has been made in controlling some of the important diseases, there is still 
far too little known about their fundamental cause and nature. An important 
advance in the understanding of regulation of basic cellular processes by 
genes, the smallest physical unit determining inherited properties, was 
made by Institute scientists with the finding that the hormone hydrocortisone 
causes an increase in protein synthesis through action at the level of the gene. 
If our understanding of cellular regulation continues to progress rapidly, 
the errors in these processes and the diseases which result from them can be 
investigated more productively. Other important fundamental research findings 
include elucidation of basic biochemical steps in contraction and relaxation 
of muscle, and confirmation of a previously suspected cellular source of 

- 8 - 
amyloid, an abnormal protein-polysaccharide substance which is the cause of a 
serious and often fatal disorder, amyloidosis. 

Scientific Communication ^ 
In a major effort to meet the scientific communication problem head-on, 
this Institute has begun a vigorous program designed to expedite cross-communica- 
tion of scientific findings and clinical data of investigators and practitioners 
through carefully planned working conferences, scientific exhibits, and 
specialized publications. An Institute activity with perhaps the most far- 
reaching implications for improving communication of scientific information 
was the inauguration, just a few months ago, of an eagerly awaited monthly 
publication. Arthritis and Rheumatic Diseases Abstracts . This journal is 
now providing American researchers and practitioners with abstracts of relevant 
literature gleaned from over 4C0O biomedical journals published throughout the 
world. We are now in the process of initiating two other such current-awareness 
journals, in gastroenterology and in diabetes, which are sorely needed for 
the dissemination of up-to-date scientific information, 

* * * * 

Research Training 
Any description of the Institute's work for the past year would be 
incomplete without mention of the Institute's important role in the support 
of research training. Our program to provide qualified young scientists 
v/ith opportunities for highly specialized training in biomedical research 
has contributed greatly to revitalization of many fields of research endeavor, 
and has encouraged some of our most brilliant and promising young minds to 
enter upon, and remain in, a biomedical research career. 

- 9 - 

In conclusion permit me to state that the Institute has completed a 
year in which it has advanced in all fields of its investigationSo Judging 
from the achievements of the past, I look forward to an expansion of advances 
in research in the 12 months ahead, 

Mr. Chairman, I am submitting a request for $119,203,000 as compared 
with the operating level of $113,162,000 for 1965. The proposed increase for 
1966 will provide for an estimated additional 80 research projects in arthritis, 
diabetes, gastroenterology and various metabolic diseases, and for an orderly 
extension of research training and fellowships and of our effective direct 
research efforts in our Bethesda laboratories. 

Public Health Service 
National Institute o£ Allergy aad Infectious Diseases 

List of Witnesses 

Dr. Dorland J. Davis, Director, National Institute of Allergy 
and Infectious Diseases 

accosipanied by 

Dr, Jam&s A. Shannon, Director, National Institutes of Health 
Dr> Js^es Colbert, Associate Director for Extramural Programs, 

Natioioal Institute of Allergy and Infectious Diseases 
Keaneth H. 3roii#3s Executive Officer, National Institute of 

Allergy and Infectious Diseases 
Martin J. Fuller, Budget Officer, National Institute of Allergy 

and Infectious Diseases 
B. Jo Sadesky, Financial Managesasnt Officer, National Institutes 

of Health 

Dr, Luther L. Terry, Surgeon General 
Harry L. Doran, Chief Finance Officer 

James F. Kelly, Departaent Coiqitroller 


Statement by Director 

National Institute of Allergy and Infectious Diseases 

Public Health Service 

"National Institute of Allergy and Infectious Diseases" 

Mr. Chairman and Members of the Committee: 

The National Institute of Allergy and Infectious Diseases, the direct 
descendant of the original Public Health Service research facility, is in 
its tenth year of a broadened responsibility that added allergic disorders 
to its historical interest in the infectious diseases. During this period 
expanding research efforts in immunology and in cell biology have contri- 
buted substantially to a better understanding of the infectious process 
and body defense mechanisms . 

As the new Director of the Institute, I have initiated a procedure 
designed to maintain a continuous evaluation of infectious and allergic 
disease problems and the needs for research. We hope that this approach 
will define areas of medical research on which we should direct and inten- 
sify our efforts. Contrary perhaps to common belief, we find that even in 
this advanced age of wonder drugs and effective vaccines, infectious and 
allergic conditions continue to exact a great toll in sickness and deaths. 

Each year ovei 120,000 of our citizens still die from infectious 
diseases. These include some 9,300 from tuberculosis and at least 70,000 
from pneumonia of which 10,000 are babies in their first year of life. 
Millions suffer disabling and debilitating illnesses « Tuberculosis claims 
54,000 new cases each year and nearly as many -- 38,000 in 1964 -- are 
attacked by infectious hepatitis. Some 15 million of our citizens are 
victims of allergic disorders. By far, the greatest single group of 


illnesses are the acute respiratory diseases. They are responsible for 
537o of all acute illnesses and are the ailments that most commonly demand 
the attention of a physician. 

Illness and premature deaths due to infections hit all age groups but 
the highest rates are in babies under one year of age. These deaths, through 
the accident of infection, are particularly tragic for they cut off normal 
lives that could have extended for 70 years at prese it mortality rates. 

I have selected for presentation at this time a few items that 
indicate the more important trends in our research activities. In no 
area is the importance of basic research so readily apparent as in immu- 
nology. The primary concern of immunology is to gain an understanding 
of, and the methods to control, the response of the body to foreign 
agents, be they microbes, chemicals, or tissues. Its importance is 
attested to by Congressional action in providing an additional $2,000,000 
to pursue such research during the current year. 

Perhaps the most determined efforts to understand the immune system 
are directed at finding ways of overcoming the homograf t-rejection reaction, 
the principal barrier to the successful transplantation of tissues and 
organs. In April, 1962, doctors at the Peter Bent Brigham Hospital in 
Boston, transplanted the kidney from an expired patient to an unrelated 
young man dying of chronic glomerular nephritis. This transplanted organ 
functioned well for many months and heralded an intensive effort on the 
part of surgeons, immunologists, biochemists and pathologists to perfect 
techniques that would offer prolonged life to many unfortunates. Necessary 
surgical skills have been perfected but uniform success awaits a better 


understanding of tissue rejection and methods to overcome it. Foreign 
tissue, eog. kidney or skin from any human other than an identical twin, 
is rejected because the body treats it as an antigen and makes antibodies 
against it just as if it were from a totally different species c Different 
antigens appear to be a part of our individuality. Therefore, in tissue 
transplantation it will be necessary to match as closely as possible the 
tissue of donors and recipients much as we now match blood groups for 
transfusions o In the meantime, partial success is achieved with human 
kidney transplants by the aid of drugs that suppress the formation of 
antibodies against foreign tissue. 

We are supporting and conducting a coordinated broadly conceived 
program of research in basic immunology and related studies pertaining 
to organ transplantation o Designed with the advice of our National 
Advisory Council and other experts in this field, the program emphasized 
methods for tissue and cell typing, suppression of the host's immune 
response to the graft implant, and an understanding of the immune events 
at the cellular level. 

Other immunologic investigations concern diseases of previously 
doubtful cause now shown to be the result of autoimmune reactions. In 
these disorders a person becomes hypersensitive to his own cells. 
Myasthenia gravis (a neuromuscular disease), allergic thyroiditis, and 
systemic lupus erythematosus (a gradually developing fatal affliction, 
especially affecting young women) are some of these conditions now under 
investigation by Institute and grantee scientists. 


Allergies to pollens, chemicals and drugs receive attention. Hyper- 
sensitivity to penicillin is one of the most prevalent problems; about one 
in 50-60 treated persons risks a reaction which can be as severe as death. 
A simple practical test to determine if a person is dangerously sensitive 
to such a drug has been developed at Washington University by a research 
career development awardee of the Institute. The test reduces by 25 times 
the incidence of penicillin reaction by identifying in advance hyper- 
sensitive patients. 

Viruses now constitute the greatest challenge to those seeking the 
cause and control of acute infections and also of many chronic diseases 
such as cancer and neurologic disorders. One of our major efforts continues 
to be directed at the control of viral respiratory diseases. They range 
from the common cold -- man's most frequent illness -- to severe and fatal 
pneumonias . 

We continue to accumulate detailed knowledge of the many agents res- 
ponsible for acute infections and their natural history -- a necessary 
prelude to attempts at imnunoprophylaxis and eventually we hope chemotherapy. 
Through the vaccine development activity, the Institute directs intensive, 
sharply focused work on new viral vaccines. One line of investigation has 
resulted in purifying and concentrating viral antigens and in devising 
better methods of identifying the fraction that stimulates immunity. For 
example, present cooperative work with Oak Ridge National Laboratory 
scientists on the high speed zonal centrifuge promises more potent immunizing 
products for several respiratory viruses. In other studies we are testing 
in humans vaccines against certain adenoviruses that are responsible for the 
more serious respiratory infections. Results thus far with an experimental 

live vaccine given by mouth against type 4 adenovirus infection (a common 
recruit disease in certain military camps) have been most promising. There 
is an urgent need also for a vaccine against the respiratory syncytial virus. 
In children, this agent causes over 25 percent of bronchiolitis, 14 percent 
of pneumonia, and 10 percent of other acute respiratory diseases. Most 
children are attacked by this virus before they are four years of age. 

But the production of an effective respiratory viral vaccine is 
perhaps as complex, difficult, and time-consuming as any other activity in 
biomedical science. Many distinct agents can produce upper respiratory 
diseases, and vaccination against one will not afford protection against 
the others. Some viruses mutate, increasing the difficulty of developing 
vaccines against them. It was a mutant form of virus that caused the world- 
wide outbreak of Asian influenza in 1957-1958. Adenovirus presented a new 
difficulty when it was found that some of the 31 known types produce tumors 
in experimental animals. This opened the question of their possible role in 
the cause of cancer and the safety testing of adenovirus vaccines. It has 
also provided new insight and ways of examining how viruses induce a normal 
cell to change to a tumor cell. 

The idea that cancer is caused by viruses received scant attention until 
very recent years, for want of adequate knowledge and technology. Now it is 
clear that viruses are important causes of a variety of cancers and leukemias 
in lower animals. 

Various recently determined facts of molecular biology now provide the 
basis for further study of the relationship of viruses to tumor formation. 
For example, some experimental animal tumors induced by viruses contain 
antigens of the virus long after the virus is gone from the tumor tissue. 
This suggests that some of the virus genetic material (nucleic acids) 

remain as footprints in the tumor cell. This demonstration of biochemical 

similarity, or homology, of viral and tumor cell nucleic acids (DNA or RNA) 

indicates that we may eventually be able to recognize particular viral 

genomes associated with human cancer. We may also be able to test the 

potential of human viruses to cause cancer by determining what similarity 

their genetic structure has with the DNA of cancerous cells. Experimental 

evidence also suggests that viruses may exchange genetic material and thus 

hybridize to alter their properties. Thus, new knowledge of how viruses 

penetrate cells and then control their genetic and growth functions will 

lead to useful measures for management of many diseases. 

Along a different line and involving a relatively new concept, Insti- 
tute scientists have contributed significantly to opening another front in 
virology in the studies of latent and chronic or "slow acting" viruses. 
Investigation of certain degenerative nerve diseases in animals has proven 
them to be due to viruses with long incubation periods. For example, scrapie 
in sheep now under study at the Rocky Mountain Laboratory, takes approximately 
one-half of a normal animal lifetime to develop clinical manifestations of 
disease. These results have motivated scientists to take a new look at 
some of the chronic diseases of man, especially such nervous system diseases 
as multiple sclerosis or amyotrophic lateral sclerosis, from the standpoint 
that they also may be the result of long term viral infections. The study 
of these diseases requires extensive animal facilities and great patience 
on the part of the scientists to wait out the long incubation periods, and 
to develop new means for revealing the presence of virus, which may not 
always be demonstrable by conventional methods. 

Next to influenza and other respiratory ailments, the group of virus 
diseases most widely spread throughout the world are those caused by the 

arthropod-borne (arbo) viruses and transmitted by insect vectors. Our most 
intensive direct effort in arboviral research is based in the Middle America 
Research Unit (MARU) . This field laboratory in the Canal Zone is operated 
by this Institute in collaboration with the Walter Reed Army Institute of 
Research, and is located in an area where arbovirus diseases exist the 
year around . 

MARU's principal research effort has been the investigation of 
hemorrhagic fever in Bolivia. MARU is one of the U.S. and Bolivian agencies 
composing the Bolivian Hemorrhagic Fever Commission in conjunction with the 
Alliance for Progress. Hemorrhagic fever, a severe disease characterized 
by internal bleeding and tremors, had a fatality rate of 20 percent as it 
swept through several small towns in northeast Bolivia. Last year, the 
research team isolated the causative virus from cases in San Joaquin, a 
small town in the main epidemic area. This year, epidemiological studies 
incriminated a rodent, Calomys callosus , as the most probable source of 
human infection; systematic trapping and poisoning eliminated the rodent 
from the town and human cases ceased. Although this outbreak has been 
stopped, continued studies are needed to find the means of transmission and 
the natural reservoir of the virus. 

Several other subjects deserve brief mention. Tuberculosis still 
resists modern medical assaults. The Institute supports several projects 
directed toward a vaccine but work at Rocky Mountain Laboratory and the 
Montana State University should be especially cited. Here scientists have 
developed a killed antigen from the well known BCG strain of the tubercle 
bacillus that is used for vaccination in a live form. Antigenic material 
isolated from the bacterial cell wall by the Montana workers is highly 


protective in experimental animals, stable, and economical to make. It seems 
to have reduced capacity to sensitize » If so, it would be of great value in 
preventive medicine. 

Effective treatment of viral infection with chemical or biological com- 
pounds has come closer to actuality with new knowledge of the chemistry of 
the cell and virus and the development of compounds that inhibit virus multi- 
plicationo Keratitis caused by herpes simplex virus is now effectively treated 
with lUDR (5-iodo-deoxyuridine) . Smallpox can be prevented or ameliorated by 
thiosemicarbazoneo Adamantine is reported to have prophylactic activity 
against influenza. Interferon, a protein product of the infected cell holds 
promise in experimental work, but has not yet been developed for clinical use „ 

A newly appreciated aspect of present day virus research is the impor- 
tance of facilities (sterile rooms, cabinets) to contain viruses under experi- 
ment and to keep them uncontaminated by other strains or their components. 
Each virus laboratory now must handle dozens of strains in culture for detailed 
studies of identification. Without proper shielding from unwanted contaminants, 
costly errors may occur. Infected animals, the most common source of trouble, 
often require specifically designed cages and animal quarters. Containment 
equipment is equally important to protect scientists from dangerous viruses 
such as oncogenic varieties or the highly infectious arboviruses. 

The 1966 request for the National Institute of Allergy and Infectious 
Diseases is $74,987,000, including $350,000 for Gorgas Memorial Laboratory. 
A comparable operating level for 1965 is $69,927,000. The 1966 funds requested 
provide a net increase of $2,540,000 for research grants; $561,000 for fellow- 
ships; $820,000 for training grants; $789,000 for direct research; $260,000 
for collaborative studies; $57,000 for review and approval of grants, and 
$33,000 for program direction. 

Public Health Service 
Hational Institute of Neurological Diseases and Blissdness 

List o£ Witnesses 

Dr. Richard Mas land, Oirectorj National Institute of 
Heurological Diseases and Blindness 

accompanied by 

Dr. James A« Shannon, Director, Hatioiaal Institutes of Health 
Dr. Bldon L. Eagles, Assistant Director, Natiomal Institute 

of Neurological Diseases and Blindness 
Sckart Wipfj Executive Officer » National Institute of 

He^rological Diseases and Blindness 
Robert L. Sithens, Budget Officer, National Institute 

of Neurological Diseases and Blindness 
B. J. Sadesky, Financial Management Officer, National 

Institutes of Health 

Dr. Luther L. Terry, Surgeon General 
Harry L. Doran, Chief Finance Officer 

James F. Kelly, Department Comptroller 


Statement by Director 

National Institute of Neurological Diseases and Blindness 

Public Health Service 


"National Institute of Neurological Diseases and Blindness" 

Mr. Chairman and Members of the Committee: 

I would like to outline some of the specific steps which the 
Neurology Institute has taken this year to accelerate its attack on 
neurological and sensory disorders. 

Program Planning 

New mechanisms have been developed in the National Institute of 
Neurological Diseases and Blindness which we believe will increase the 
rate 5 quality, and application for the benefit of patients of research 
findings in neurology. Two of these are the organization of special 
planning committees, and the establishment of scientific information 
Special Planning Committees 

A number of special planning committees, organized by the Institute's 
Advisory Council, provide for total review and program planning in the area 
of the Institute's responsibility. An outstanding example is the 
Subcommittee on Cerebrovascular Disease organized jointly with the National 
Heart Institute. 

This small working committee of representatives of the two Institute 
Councils and other consultants has been carefully laying the foundations 
for a more aggressive national program to combat strokes. The committee 

has organized a series of workshops on each of the major problems and has 
published summaries of these deliberations. Also, two national symposia 
on strokes have been sponsored. 

Working with the National Library of Medicine, the committee has 
published a bibliography on strokes and related brain disorders. Valuable 
information concerning national research needs in this field has been 
assembled and the committee has suggested programs to meet these needs. 

The Institute's development of a series of clinical research centers 
for cerebrovascular disease, its cooperative study of brain aneurysms, the 
field trials of anticoagulant drugs, and numerous other activities have 
been carried forward under the surveillance of this task force. With their 
assistance, the Institute has moved forward its stroke program on a number 
of fronts. 

Another Council planning committee, the panel on evaluation of 
clinical therapy, was established last year and has developed a number of 
important projects. Most significant is the cooperative study of the 
effectiveness of ACTH in multiple sclerosis. Using the protocol which had 
been developed by the working committee organized at the Institute- 
sponsored conference on the evaluation of therapy in 1960, a cooperative 
trial of treatment is now being launched. This panel has also reviewed 
plans for a cooperative study on treatment of epilepsy and a similar 
project for the investigation of proposed treatments for muscular 

This year the Institute organized similar working groups for a 
more precise effort against the blinding diseases and against the disorders 
of speech, hearing, and human communication. These task forces, composed 

of Council members and other consultants, will investigate the state of 
knowledge in each field and identify areas needing special attention. 
Disease Study Units 

Under the guidance of these planning committees, the Institute also 
has been developing a number of projects to study diagnostic procedures, 
evaluate treatment, make epidemiological studies, and investigate the 
"life history" of disease processes as they affect patients of different 
ages. The method involves the focus of each project on a specific disease 
or disease problem by means of a few separately located "disease study 
units" with in-patients or out-patients. In addition to studies on 
aneurysms, myasthenia gravis, multiple sclerosis, epilepsy, and speech 
and hearing, investigators are also concerned with acute head injury and 
cerebral palsy. 
Information Centers 

The Institute's establishment and support of centers for scientific 
information and program analysis will improve the surveillance of the 
national research effort in specific fields. These scientific information 
centers are being established in the great universities where the competence 
and judgment of senior scientists can be relied upon and the necessary 
technical competence is available. 

The center on Parkinsonism and related disorders, established at 
Columbia University, represents the first of these units. During its 
opening year, the center has developed strong, broadly based research 
and information exchange programs, and has sponsored an important inter- 
national conference focused on the control of involuntary movement. 

- 3 

Two other centers are in the planning stages. These three centers, 
working in close cooperation with the National Library of Medicine and a 
small program analysis unit at Bethesda, constitute the framework on which 
the Institute's coordinated program for scientific information exchange is 
being expanded. 
Research on "Slow Viruses" 

This past year, the Institute has been expanding its search for 
"slow" virus agents in connection with such diseases as multiple sclerosis, 
amyotrophic lateral sclerosis, Parkinsonism, kuru, and certain forms of 
epilepsy and encephalitis prevalent in childhood. Some of these studies 
are being conducted at the Institute's laboratory at Patuxent. Certain 
"slow" viruses are known to be responsible for neurological disorders in 
animals. In order to search for such agents in human disease, a number of 
animals have now been inoculated with material from human patients. 
Neurological symptoms caused by slow viruses may take a number of years 
to develop, and to date no animals in this laboratory have shown evidence 
of disease thus contracted from human material. 

The Institute sent a mission to the Soviet Union in May 1964 to 
investigate reports that viruses had been isolated from patients with 
amyotrophic lateral sclerosis (ALS) and other similar diseases. This 
mission has been cooperating with Soviet scientists in an effort to see 
whether their observations can be verified. To date, however, the 
Americans are not convinced that a viral cause of ALS has been proven 
by the Soviets. In December, a small group of internationally-known 
experts met in Bethesda to review research relating to "Slow, Latent, and 
Temperate Viruses" and to chart future needs. 

4 - 

Instrument Development 

Increasingly, scientific knowledge has moved forward as a result 
of new instrumentation and improved scientific techniques. The Institute 
has employed industrial conv.., J^cts and is exploring the means of effective 
utilization of professional and technical competence in industrial 
organizations . 

This year, the Institute organized a series of small conferences 
among representatives from biomedical research and industry to determine 
the capability within industry for the development of certain highly 
needed instruments. One conference concerned the development of automatic 
instrumentation to test for phenylketonuria and other inborn errors of 
metabolism known to cause mental retardation. Another conference among 
radiologists and X-ray equipment producers considered improvements of 
techniques for the detection of cerebrovascular disease, brain tumors, 
and other intracranial pathology. 
Statistics on Blindness and Deafness 

Because of the lack of accurate information on the causes of 
blindness, its overall incidence and prevalence, and the distribution of 
disorders of vision, the Institute enlisted the cooperation of several 
voluntary and official agencies to organize the Model Reporting Area for 
Blindness Statistics. This association now includes 10 States which 
maintain a State-wide register of blind persons. The first tabulations 
for the Model Reporting Area are now available, and with the anticipated 
addition of new States, more accurate estimates on national distribution 
of blindness will soon be available for the first time. 

The methodology has been developed for a similar project to obtain 
data regarding the causes and frequency of deafness. 

- 5 

Collaborative Perinatal Project 

The Collaborative Project (Collaborative Study on Cerebral Palsy, 
Mental Retardation, and Other Neurological and Sensory Disorders of Infancy 
and Childhood) , now in its sixth year, is already providing valuable 
information regarding the impact of perinatal factors on the developing 
nervous system. For example, nearly twice as many babies had neurological 
impairments when delivered by elective Cesarean surgery under general 
anesthesia as those delivered naturally. Furthermore, general anesthesia 
for the mother was far more damaging to the Cesarean-born baby than 
regional anesthesia. 

Slightly more than one percent of all Project pregnancies are 
affected by premature separation of the placentae. Few children of such 
pregnancies survive the first year. Of those who do survive, nearly 
4 percent are found to have neurological abnormalities at one year of age. 

Investigators in the Project also have reported that simple surgical 
correction of incompetent cervix, which can reduce perinatal death by more 
than 50 percent, can also result in a threefold reduction of subsequent 
neurological impairment to the baby at one year of age. 

Collaborating investigators have succeeded in defining more 
accurately the degree of risk to the developing infant of toxoplasmosis, 
of "salivary gland virus" disease, and of German measles. They are 
contributing to the development of improved diagnostic and therapeutic 
measures for these conditions which are proving to be of far greater 
prevalence than had previously been recognized. 

Because of the urgent need for computer services and processing 
facilities, the Institute has supplemented Bethesda services through 
industrial contracts. It is anticipated that these newly available 

contracts will permit acceleration of the assembly of Project data on 

approximately 50 separate studies over the next year. 


An essential element in the Nation's medical research program is 
an adequate supply of trained scientists. The increasing complexity of 
medical research technology has lengthened the required training. For 
these reasons, a major concern of the Institute has been the development 
of a training program where research techniques can be learned, and 
scientists prepared for lifetime careers in research. The program has 
been directed toward the training of professional personnel for laboratory 
or clinical research in four general areas--vision, human communication, 
neurology, and neurosurgery. 

The Institute is now supporting over 225 training programs with 
1,300 individuals in training, and an additional senior group of 390 
selected individuals within the fellowship and career award program. 
A crude index of the impact of this program is the remarkable increase in 
the number of men entering positions in full-time teaching and research. 
During the last 3 years, the number in neurology and pediatric neurology 
has increased from 139 to 349; in neurosurgery from 58 to 132; in 
ophthalmology from 64 to 150; and in otolaryngology from 31 to 81. 

Although these figures are small in terms of total manpower in 
these fields, the impact is great. These scientists, highly trained for 
teaching and research, represent the essential base upon which future 
advances--both in the science and the practice of neurology--must be built. 
Specialized Centers for Research 

With the increasing availability of trained scientists, it has been 
possible for the Institute to establish 23 specialized centers for neuro- 
logical and sensory research. Located within leading medical centers, 

clinical investigators and basic scientists from many disciplines are 
coordinating their attack on many unsolved problems of disease. These 
centers include three in strokes, two in epilepsy, one in Parkinsonism, 
six in clinical neurology, five in basic neurology, and six in neurosensory 
areas including vision, speech, hearing, and equilibrium. Of these last 
six, two are in ophthalmology exclusively; one in ophthalmology and 
neurology; one in hearing, vestibular research, and ophthalmology; and 
two in communicative sciences. 


The request for 1966, Mr. Chairman, is $92,153,000 which provides 
for increases in research and training grants as well as increases in 
direct operations. Of the $76,700,000 for grants, the major portion, 
$58 ,890,000, is recommended for research. To aid in alleviating the 
shortage of investigators, $15,457,000 is included for training and 
$2,353,000 for fellowships. 

For direct operations of the Institute of $15,453,000, the major 
amount, $7,963,000, again is for research, and $5,196,000 is for collab- 
orative studies. The remaining $2,294,000 would include the necessary 
review and approval of grants ($1,832,000), intramural training ($65,000), 
and administration ($397,000). 

Such an investment in research of this Institute can be expected 
to provide a rich return in improved American health and economic 
productivity. The potential for progress in neurological and sensory 
disease research from 1965 to 1970 is much greater than it has ever been 
and this budget will further the achievement of the potential. 

- 8 

Public Health Service 
General Research Support Grants 

List of Witnesses 

Dr. Frederick L. Stone, Acting Chief, Division of Research 
Facilities and Resources 

accompanied by 

Dr. James A. ShanaoG, Sirector, National Institutes of Health 
Dr. J. H. U. Brown, Assistant Chief for Operations, Division 

of Research Facilities and Resources 
Gordon J. Klovdahl, Executive Officer, Division of Research 

Facilities and Resources 
Esasa Lou Akers, Budget Officer, Division of Research Facilities 

and Resources 
B. J. Sadesky, Financial Management Officer; National 

Institutes of Health 

Dr. Luther L. Terry, Surgeon General 
Harry L. Doran, Chief Finance Officer 

James F. Kelly, Department Comptroller 


Statement by Acting Chief 

Division of Research Facilities and Resources 

National Institutes of Health 

Public Health Service 


"General Research Support Grants" 

Mr. Chairman and Members of the Committee: 

I welcome this opportunity to present to you our proposal for the 
general research support program for 1966. 

Background and Purposes 
This program, authorized in 1960 by Public Law 86-798, provides support 
for the otherwise unmet health research and research training needs within an 
entire institution. Awarded on a continuing basis, these grants complement 
rather than supplant other types of research support. Their general nature 
enables administrators to exercise greater scientific responsibility for an 
entire research effort, or specific parts of it, and therefore to correct 
imbalances of an institutional nature that may have developed. The flexibility 
of these grants makes possible the exploration of new, unorthodox ideas not 
yet ready for scrutiny by scientific advisory groups of granting agencies. 
And through their support of centralized, common research resources such as 
laboratory animal quarters, general research support grants improve the envir- 
onment in which research takes place. 

To summarize briefly the program development, the first awards, totalling 
$20 million, were made in January 1962 to 153 health professional schools- 
medical, dental, public health, and osteopathy. The following January, the 
program was extended to schools of pharmacy, nursing, and veterinary medicine 
as well as to hospitals, research institutions, and other nonprofit organi- 
!..-,f-f .<,><, hoavily engaged fn ba.a.TtK-*eJatcd research. The total expended was 


$30 million. During 1964, $35 million in general research supt^ort funds was 
awarded to 262 health professional schools and to other institutions. 

Though the main characteristic of these awards is the latitude in 
their use, at the outset of the program the Public Health Service and the 
grantee institutions themselves felt the funds could be used to special 
advantage in the following areas: 

— support of new and pilot research projects which show 

promise of developing into research that would merit support 
from granting agencies 
— stabilization of salaries making it possible to both retain 

and recruit high-calibre professional and technical staff 
— provision of central resources such as animal quarters, computers, 
electronic engineering shops and other auxiliary research service 
--support of research projects of less than $2000 and part-time 
research training. 

Program Evaluation 
The program has now entered its fourth year of operation. In accordance 
with the expressed wishes of the Congress, a preliminary evaluation of the 
program has been initiated to determine how effectively the program objectives 
have been served. It was considered essential that an evaluation of this 
nature be made by an impartial organization and one whose reputation in the 
scientific community is above reproach. Consequently, the assessment is 
being made by the National Academy of Sciences/National Research Council. 

While examining broad aspects of the program, including accountability 
and fiscal and grants management responsibility in the institutions, special 
attention is being given to assessing the impact of these funds on the total 
pvogiatii of health research and vecearch training within the medical school 

or other grantee institution. The assessment of this impact is of particular 
importance because of the widespread distribution of these general research 
support funds to institutions both small and large, private and public, 
academic and non-academic, young and long-established, in all, more than 262 
throughout the United States; and also because of the unprecedented degree 
of responsibility permitted officials in administering these funds and allo- 
cating them to support health research projects and training programs. 

Those who are conducting this impartial evaluation are especially 
interested in measuring the extent to which the program has stimulated new 
activities, the expansion of current programs, and the recruitment of out- 
standing faculty and advanced students. Also being assessed are the ways 
in which those funds have efficiently and effectively improved the quality 
of research by making possible new and improved central research resources 
used in common by many scientists. 

Another area being evaluated is the effectiveness of methods used by 
schools and others to determine choices and to set priorities for expenditures 
of these general research support funds. There will also be an effort to 
determine how compatible are the National Institutes of Health objectives and 
administration of this program with the institutions' objectives and plans 
for their own scientific development. The NIH will be especially interested 
in the assessment of the program's ability to expand into new areas and in 
new directions. 

This initial survey will provide not only a better understanding of 
the way in which these flexible funds have contributed uniquely to the 
catalytic growth and development of health sciences and research training, 
but also will provlrfe guide posts for future developments In the basic program. 

Institutional Uses of Program 
During the three years the program has been in operation, the Division 
of Research Facilities and Resources which administers the program has been 
accumulating and analyzing a considerable amount of data essential to its 
administration. Medical schools have received the largest share of these 
funds: $16.5 million in 1962 out of the $20 million appropriated, and in 
1964, about $20 million out of the $35 million appropriated. Hospitals 
ranked second, receiving $2.9 million in 1963, the year in which they first 
became eligible for support, and $4.3 million in 1964. 

Most of the funds have been used flexibly to support new and pilot 
research projects. Medical schools employed 33 per cent of their general 
research support funds in this way; dental schools used 44 per cent; and 
all other institutions more than 50 per cent. 

More than 3000 research projects, most of them modest in scope, were 
supported in calendar year 1963, of which more than 1050 were new research 
projects. Behind these figures lies a most important aspect of the general 
research support program, namely, the early discovery and prompt cultivation 
of new research talent. Numerous schools have indicated that top priority 
for these funds is given to younger faculty members with original ideas. All 
too frequently the young investigator's research efforts are dictated by the 
research interest of a senior investigator with whom he has aligned himself 
because the scientist had adequate support and needed another pair of hands. 
As a result, a promising young investigator may continue a line of research 
not particularly interesting or challenging to him but which he is reluctant 
to give up because he has invested so much time and effort. By supporting 
the young, promising investigator at the very outset and enabling him to 
pursue his own ideas, tho.c general v^.-arch support fund, perform an 
•Invaluable function. 


In 1963, more than 4500 professional and technical personnel received 
whole or partial salary support from the general research support funds. 
Reports indicate that numerous departments have been established and headed 
by distinguished scientists whose recruitment was possible because of the 
immediate availability and flexibility of these funds. 

In addition to the support of staff, the funds enabled more than 2600 
persons to receive research training in 1963. 

Central research facilities such as animal quarters and computer 
resources accounted for approximately 18 per cent of total expenditures in 
1S63, Central facilities where experimental animals are kept under excellent 
conditions, well supervised and staffed by trained personnel, have greatly 
enhanced the quality and validity of research findings. 

Extensions of Program 

In Fiscal Year 1965 the Congress appropriated funds specifically for 
extending general research support awards to academic institutions other than 
the health professional schools. By this action a vital segment, important 
in size and qualtiy, of the national health research effort now is included 
in the program. 

Support provided to these recently included universities will strengthen 
not only their own programs and activities in the health sciences, but will 
also stimulate additional activities and programs in the communities, states, 
and regions where they are located. One goal in providing these funds to the 
universities is to bring the traditional health sciences in closer touch 
with mathematics, engineering, the behavioral sciences, and newer areas 
related to biology and medicine. 


Part of the Nation's future need for well-trained, creative scientists 
and teachers can be met by providing institutions with flexible funds for 
planning long-range development in the health research and training areas, 
for initiating training programs and research projects, and for improving 
the capability for conducting significant research in complex fields. The 
universities across this country which will receive these grants have 
demonstrated some degree of commitment to and accomplishment in the health 
sciences, and therefore can be relied upon to recruit and train the investi- 
gators of tomorrow, while at the same time advancing medical research in 
today's world. 

A further major development in the general research support program is 
now in the planning stages. In Fiscal Year 1965, the Congress authorized the 
NIH to use a portion of the general research support funds for the advancement 
in the health sciences of selected institutions. Entitled the "Health Sciences 
Advancement Program," it will strongly complement but not duplicate the 
programs of the National Science Foundation and the National Aeronautics and 
Space Administration, both of which have university support-type programs. 
Lack of duplication results, of course, from the fact that awards under the 
NIH program will be restricted to the support of health sciences programs. 
Above all, this new program will require close collaboration between the NIH 
and the institutions to insure the highest degree of cooperation and planning, 
execution and evaluation. 

The Health Sciences Advancement Program offers an important mechanism 
by which the expressed wishes of the Congress can be implemented for the 
improvement of existing centers and the development of new centers of excel- 
lence in the health sciences. Though a start is being made in 1965, the 
program, because of the complexities Involved, cannotbe fully developed until 


1966. First there must be critical evaluation of various plans before policies 
and guidelines can be established. Some of the most promising plans now being 
studied by the staff of the General Research Support Branch of this Division 

1. Health sciences advancement awards would be made: a) to institutions 
of outstanding quality which heretofore have not directed their efforts toward 
biomedical research and research training, but which have specific plans for 
initiating programs in these vitally important areas; b) to strengthen 
selected research and research training areas or departments in otherwise 
excellent medical and other health professional schools; c) to strengthen 

the research training in basic sciences in those medical schools which geog- 
raphically are separated from the main university campus; d) to strengthen in 
appropriate fields the biomedical research and training programs of those 
universities which geographically are separated from their medical and other 
health professional schools and affiliated medical center, 

2. Health sciences advancement awards would be provided: a) to support 
two or more major schools in the cooperative development of special programs 
that would financially overburden a single institution and that would require 
special qualified personnel; b) to support new medical, dental, and other 
health professional schools on the premise that, from their beginning, an 
orientation toward modern research and research training would enrich medical 
research and scientists for the entire next generation. 

3. Health sciences advancement awards would be used to establish 
model centers for health research and research training in settings where 
there is evidence of high quality of faculty, research, training opportunities, 
and facilities. These centers couLd be integrated with Independent colleges 


within the same geographic areas to facilitate exchanges of faculty and 
students, and in general provide the best possible training in the biomedical 
fields to both graduate and undergraduate students. 

Potentially, the Health Sciences Advancement Program can develop strong, 
new centers of health science research and training throughout the country. 

In summary, the general research support program now has three major 
approaches to strengthening and improving biomedical research: first, the 
continued provision of flexible funds to health professional schools and 
research institutions; two, the extension of these funds to academic insti- 
tutions including graduate schools and universities which will, among other 
things, bring closer ties among traditional health sciences and the sciences 
of mathematics, engineering, behavior, and newly developing fields; and three, 
the support of other institutions showing promise of long-range development 
as dynamic centers where the health sciences may take giant strides. 

In the first three years of the general research support program, 262 
schools and research institutions received $85 million in these funds. The 
1965 Appropriation Act provided $45 million for this purpose. 

Mr. Chairman, the request for the general research support program is 
a total of $45.2 million. Of this amount, $39.2 million will fund the current 
program of general research support for health professional schools, hospitals, 
and research organizations; $5 million for continuation of the support to 
academic institutions other than the health professional schools; and $1 million 
for further development of the Health Sciences Advancement Program. 

Bffibli© Igall;^ Service 
Graats fer CosistriaefsieB of Eealth leseerch Faeilitiss 

List @f Mi£mss@s 

Dr. Frede^iek L. StoBe.^ Aati^ Chief » Division @£ R®s@S3reh 
Facilities aod Ress^rees 

^es@a^affli@d bj 

Dr. J3is@s A« Shasssoffi, Dixector, National Institutes of Health 

Dre J» le Uo Bro^»ii» Assistant Chief for Opmx&ttons^ Di^risiDm 

of Isssareh Fasllitiss and Resomrees 
S®rd@si Je Elovdahl, Executive Officer^ Diirisioa of Bfisearch 

Facilities and Resources 
SBtea I@u Alters, Budget Officer $ Bi^isiss^ o£ Research 

Facilities md Eeso«irc@s 
B. J. Sadesky, Fi^^cial Maoag^s^nt Offiearg lati^sal 

Institutes of Health 

Dr« Luther L« Tarry » Sffirga®© Seaaral 
Harry L. Doraa, chief Fiiiaiac@ Officer 

Jisaes F. lellys HBp&wtMB&t Controller 


Statement by Acting Chief 
Division of Research Facilities and Resources 
National Institutes of Health 
Public Health Service 


"Grants for Construction of Health Research Facilities" 

Mr. Chairman and VLembers of the Committee; 

I welcome this opportunity to speak to you about the health research 
facilities program in connection with the appropriation request for Fiscal 
Year 1966. 

This program has tvo parts. Under Title VII, Part A of the Public 
Health Service Act, the program provides grants up to 50 per cent of the cost 
of construction, large-scale renovation, and equipment. Under Part D of Title 
VII, the mental retardation research centers program, authorized by the 
Congress in 1963, provides awards up to 75 per cent of the cost of these 
specialized centers. 

Title VII. Part A 
I should like first to speak in behalf of the program under Part A. 
This program, now in its ninth year, provides matching funds up to 50 per 
cent of the cost of construction or extensive renovation, and for equipment 
of health research facilities. In 1956, the Congress authorized $30 million 
annually for three years. In August 1958, the authorization was extended for 
three more years, and in October 1961 was extended for a one-year period with 
authorization for an increased appropriation of $50 million. That same amount 
was authorized in October 1962 when the program was extended for three more 
years. Authorization for funding extends through June 1966, although no 
grant applications may be accepted after June 30, 1965. A request has been 
submitted to the Congress for ax. extension of thi^ vital construction program. 


This program is looked to as the primary source of construction 
funds for health research facilities by medical and other health profes- 
sions schools. In fact, since the program began, these schools have 
received almost $180 million in health research facilities grants. Univer- 
sities, private research institutions, hospitals, state and local health 
departments also depend heavily on these funds and have been awarded a total 
of about $140 million. This program further provides facilities that vastly 
strengthen the research capability in areas of pre-eminent concern to the 
Public Health Service such as mental health and environmental health. 

A sudden upsurge of requests for these funds resulted from the Health 
Professions Educational Assistance program, enacted by the Congress in 1963, 
authorizing grants for multipurpose buildings in new or expanding medical, 
dental and other schools. Estimates from 52 medical schools alone indicate 
their need for new facilities that will cost about $517 million. Since 
research is an intrinsic part of biomedical education today, requests ranging 
from $200 million to $250 million can be expected from these schools. 

Along with the need for more laboratories of the traditional type 
and specialized clinical research facilities, modern research requires a 
great amount of what might be called supportive space — "cold" rooms, 
separate isolation systems for virus and other research on pathogenic micro- 
organisms, biomedical engineering laboratories, special purpose animal facil- 
ities, radioactive chemical and counting rooms, and space for special elec- 
tronic monitoring systems. 

Other developments in the evolution of research facilities are high 
altitude chambers for studies of man's reaction to the stresses of flight 
and space, hyperbaric chambers for research in heart surgery and cancer. 

and biotrons in which tropical, arctic, or any other atmospheric condition 
can be simulated. Nev? techniques and modem instrvunentation in clinical 
research have considerable influence on design. Chromatographic and radio- 
isotope procedures for the study of heart disease and cancer require special 
air-conditioning and environmental control. Tissue and organ transplantation 
studies, among others, need facilities that ensure precise environmental 

Nor should we overlook the fact that along with more demands for 
health research facilities funds there has been a decrease in the amount of 
space those funds purchase today compared with 1956, When the program 
started, a million dollars bought 20,000 net square feet of laboratory space. 
Today, a million dollars buys only 16,000 net square feet, a loss equal to 
about 20 average size laboratories. 

Without question the trend today is toward large-scale multipurpose 
research construction, often designed to house scores of scientists in many 

To give you some indication of the size of health research facilities 
grants now, in 1964, there were 15 grants of $1 million or more totaling 
more than $25 million and 18 grants of $500,000 or over but less than $1 
million totaling almost $12 million. In other words, 33 grants accounted 
for almost $37 million of the $50 million annual appropriation; 69 per cent 
of the 1964 funds supported grants of $500,000 and over. 

Strongly influencing this trend toward the large research construction 
project is the fact that universities and other large institutions no longer 
expand haphazardly, but plan their building programs on five-, ten-, or 


twenty-year projections. This type of planning fosters tremendous economies 
in the biomedical as well as in other research facilities. One large 
building designed to house many departments and disciplines benefits from 
central utilities, air conditioning, heating, stairways, elevators, as well 
as centralized maintenance. 

As the first NIH program designed to improve the physical environment 
in which research took place, this program in the beginning followed the 
pattern of research project grants in that awards usually provided space and 
facilities for individual outstanding scientists. The program has moved 
away from this "personalized" concept and has broadened to an "institutional" 
concept, providing facilities that support research programs of several 
departments or of an entire institution. Ideally, a health research facility 
should be constructed around the scientific programs, should be designed to 
serve the purposes of many projects, and the interests of many scientists. 

Of 990 construction projects supported by the health research facil- 
ities program, 68 per cent have been completed, but in terms of money, they 
account for only 43 per cent of the $320 million awarded because the larger, 
more complex facilities are still under construction. The remaining already 
obligated funds of $182 million pertain to some 186 projects which are 
presently under contract or construction and 135 in varying stages of advance 
planning preparatory to award of construction contracts. 

Accounting further for the substantial increases in the size of these 
grants are the requests for costly, specialized research facilities such as 
those mentioned above together with clinical research centers, and central 
animal resources. 

In the administration of these grants, an important step was the 
appointment of a Scientific Reviei,; Committee of distinguished scientists 
in the spring of 1S6A to serve, in effect, as a "study section," to 
concentrate on the review of the scientific merit of the projects described 
in health research facilities applications, this review to include visits to 
the institution applying for a grant. As a group, the Committee discusses 
each application and makes recommendations to the National Advisory Council 
on Health Research Facilities, which, of course, on the basis of the evidence 
and its ovm judgment makes its recommendation to the Surgeon General for 
final action. 

Last year we reported to you that the Division of Research Facilities 
and Resources which administers this program had established the Office of 
Architecture and Engineering to help applicants plan their research facil- 
ities. Grant applicants have v<relcomed enthusiastically this assistance from 
these architects and engineers whose specialty is modern research laboratory 
design. This cooperative planning effort extends over many months. The 
usual major health research facilities construction project requires from 
three to six months for its planning and schematic drawings, six to twelve 
months for final working drawings, and one to two years for construction. 
Even under ideal circumstances, from the preapplication conferences to the 
final inspection of the building, as much as four years may elapse. 

In Fiscal Year 1964, the Division's architects and engineers reviewed 
almost 200 applications. As a result of their reviews of construction 
bidding documents, more than $1,150,000 of unneeded funds was saved, an 
amount that made it possible to fund six projects from the backlog of 
approved but unpaid awards. 

To bring the administration of health research facility grants more 
in line with program developments in recent years, we have instituted not 
only a more thorough scientific review of applications, but also an analysis 
and evaluation of the program to answer such questions as: l\fhat have those 
$320 million dollars in matching funds accomplished? What has been the 
impact of these facilities on the entire scientific program of an institution 
or even on a much wider community? What are the major scientific areas being 
supported by the facilities? What has been its impact economically? 

We already know that aside from this program's basic mission of 
providing facilities for the conduct of meritorious research, it has had 
considerable impact on the economy of the communities in which the facilities 
are constructed. A study made by the United States Chamber of Commerce 
indicates that a new laboratory with 100 jobs, on the average annually brings 
359 people, $710,000 in spending power, $331,000 in retail sales, and $229,000 
in bank deposits. Translating these figures into the economic impact of the 
health research facilities program, it is estimated that the facilities have 
brought raore than $220 million in spending power and over $100 million in 
retail sales to communities. There is also the economic impact on the 
construction field, the steel, cement, cables, paint, fixtures, tiles, the 
heavy equipment used in these buildings, the gasoline used to transport the 
building materials, equipment, and so on. For every job on the construction 
site, it is estimated there are two "off site" jobs. 

In addition to the $320 million in health research facilities funds 
awarded since the inception of the program for health-related facilities, 
approximately $500 million in matching funds have been provided from resources 
of the grantees and from other non-Federal sources such as foundations. 

Approximately $700 million more have been spent by the grantees for non- 
bealth-related portions of the construction, making a total of about $1.6 
billion of construction. 

Since the program began, 1,650 applications for construction, large- 
scale renovation, and equipment have been submitted requesting a total of 
about $565 million in these matching funds. Up to December 31, 1964, 1,263 
grants totaling $320 million had been awarded. 

From the very outset, this program has operated with a backlog of 
requests for more funds than were available. As the program continued, not 
only did the amount requested exceed the amount authorized, but there was a 
steady increase in applications recommended by the Council for awards, but 
for which there were no funds. The present backlog is $28,500,000, a figure 
that, based on nine years 'experience, can be expected to increase by another 
$25 million after the March 1965 Council meeting and $25 million more 
following the June 1S65 Council meeting. It is estimated that the backlog 
of approved but unfunded grants at the end of Fiscal Year 1965 will be about 
$80 million. 

A barometer of current and potential needs is the list maintained by 
the Health Research Facilities Branch of "Intentions to File Title VII A 
Applications," projects whose cost has been estimated, but which have not 
been submitted as formal applications. On the present list of "Intentions 
to File," there are about 138 projects totaling $76,927,230. 

To continue this program for another year, it is requested that the 
amount of $50 million, the amount authorized when the Congress extended the 
program in October 1962, be appropriated for 1966. 

Title VII, Part D 

In October 1963, the Congress authorized the Public Health Service 
to launch a new, many~pronged attack on mental retardation. To encourage 
greater interest among scientists, $26 million was authorized over a four- 
year period for construction of large-scale mental retardation research 
centers. The first appropriation was for $6 million for 1S64 and $8 million 
for 1965. 

These grants provide matching funds up to 75 per cent of the cost of 
construction of the centers. Applications for these large-scale facilities 
receive a dual review by the National Advisory Councils for Health Research 
Facilities and fot the Institute of Child Health and Human Development, 

Just about a year after the late President John F, Kennedy signed the 
Act authorizing these special construction funds, the first two awards were 
made. The University of Washington School of Medicine in Seattle received 
$5,7 million for constructing three new buildings and remodeling some space 
in a health sciences building. The Albert Einstein College of Medicine of 
Yeshiva University in New York was awarded $3,085,000 for a ten-story building. 

These two awards culminated almost a year of intensive planning and 
collaboration with, on one hand, the two universities and, on the other, the 
Division of Research Facilities and Resources and the National Institute of 
Child Health and Human Development. 

To provide funds for additional mental retardation research centers, 
it is requested that the full $6 million authorized by the Congress be 
appropriated for 1966. 

umAT^, tequisitions Mi. 
National Institutes of Heslttl 
Building 10 



m LlBRARy 


^ Amazing Research. 


10 Center Drive 

Bethesda, MD 20892-1150 


paiNTEDlNU.S * 



4 0128 7445